Yourlawyer.com (Foradil News)

FDA Panel Wants Restrictions on Two Asthma Drugs

Fri, 12 Dec 2008 00:00:00 -0800

A U.S. Food and Drug Administration (FDA) panel has called for restrictions on two asthma treatments: Serevent and Foradil. Both belong to a class of drugs known as long-acting beta-agonists. Both contain a drug that relaxes muscles around airways, said WHEC TV, but may also mask symptoms that can prompt deadly asthma attacks. Although the expert 27-member panel found Serevent and Foradil drugs present greater risks than benefits and should not be used in the treatment of asthma, the inhaler drugs will likely not be pulled, said WebMD Health News.

The panel suggested the FDA alert physicians to not prescribe Serevent and Foradil as a stand-alone treatment for patients of any age, said WebMD; however, the drugs’ use in chronic obstructive pulmonary disease (COPD) remains unaffected. The panel backed Symbicort and Advair, finding the benefits were greater than the risks, added WebMD.

NBC noted that with 20 million Americans suffering from asthma, it is critical they receive appropriate treatment at the first sign of an attack, noting that the panel was reviewing the benefits and risks—such as hospitalization and death—of a variety of asthma medications.

NBC pointed out that Advair, Serevent, Foradil, and Symbicort are all long-lasting medications that might reduce reliance on rescue inhalers. But, an FDA study found that long-lasting drugs present a two-to-seven times greater risk over other medications for severe complications and death, especially in women, African-Americans, and children under 12. Doctors recommend, said NBC, that these drugs be used in collaboration with inhaled cortico-steroids, which treat inflammation. In Symbicort and Advair, the steroid is built in. Advair was the only one of the four drugs with no increased risk, reported NBC.

Angel Waldron of the Asthma and Allergy Foundation of America told NBC that, “Removing them or limiting access to them would be setting us back about fifteen years in asthma care,“ but not all experts agreed. One recommended Serevent and Foradil be pulled and all four banned for children. Another felt the benefits “far outweighed” the risks, said NBC, which noted of 60,000 patients studied, 20 suffered asthma-related deaths.

Medical guidelines and the drugs' labeling recommend long-acting beta-agonists only be used with inhaled steroids to minimize airway inflammation; the combination lowers risks to levels experts find acceptable, reported WebMD Health News. But studies reveal most asthma patients tend not to use inhaled steroids as prescribed when taking them separately from beta-agonists and patients receive relief from beta-agonist inhalers, leading many to use them alone—a practice called monotherapy—which raises the drugs’ risks, according to the FDA studies, said Web MD.

"I think the label should be greatly strengthened to say that monotherapy for asthma should basically be contraindicated" for Serevent and Foradil, Daniel Notterman, MD, a member of the advisory panel from the department of molecular biology at Princeton University, told Web MD Health News.

Notterman was not alone, and the FDA panel agreed with him in a 17-to-10 vote, saying Serevent and Foradil’s risks outweigh benefits when used alone. The panel found voted unanimously that neither drug be used in younger children four to 11 years old, said Web MD Health News.

"The data is that single use is dangerous," David Schoenfeld, PhD, a panelist and professor of medicine from Massachusetts General Hospital, told Web MD.

Because Advair contains both a beta-agonist and steroids, thus reducing the risk of airway passage inflammation, the pane backed that drug. However, there was disagreement among panel members regarding Advair’s use in children. The fourth drug, Symbicort, is not generally prescribed for children said Web MD.

FDA Considers Heart Risks of Serevent, Foradil, Advair and Symbicort

Thu, 11 Dec 2008 00:00:00 -0800

One expert estimates that long-acting beta-agonists (LABAs) - a class of asthma drugs that includes Serevent, Foradil, Advair, and Symbicort - might be responsible for about 14,000 deaths, Reuters is reporting. The comments were part of a confrontational meeting between the U.S. Food and Drug Administration (FDA) and an advisory panel discussing how to handle increased risks experienced with the inhaled asthma medications called LABAs, said Reuters,

LABAs are used by millions of patients, many of whom are children, noted Reuters. Advair and Symbicort use a LABA with an inhaled steroid; Serevent and Foradil (marketed in the U.S. by Schering-Plough Corp.) only contain LABAs, said Reuters.

Reuters explained that asthma, a chronic disease with symptoms that include restricted breathing and wheezing, can be fatal when untreated or uncontrolled. About 20 million Americans suffer from asthma, according to the National Institutes of Health, said Reuters. LABAs help relax airways to prevent the spasms that cause the attacks and are accompanied with warnings about a link to asthma-related deaths based on findings from a Glaxo study shut down in 2003, said Reuters.

FDA reviewers argued that LABAs should never be prescribed to pediatric asthmatics and asked for revocation of Glaxo's Serevent and Novartis AG's Foradil for all asthma patients, regardless of age, reported Reuters. "We now know with high certainty that LABAs increase asthma mortality. Do the health benefits justify that?" asked FDA drug safety reviewer David Graham, said Reuters, who added that Graham has publicly criticized the FDA’s managing of drug risks. Graham agued that LABAs benefits do not justify its risks, saying that he’s seen little improvement in asthma patients treated with LABAs, noting that as many as 14,000 deaths since 1994 can be linked to LABAs.

The FDA reviewed over 100 clinical trials that involved about 61,000 patients and found that for every 1,000 patients treated with a LABA, nearly three such patients experienced serious asthma-related complications, which included hospitalizations and death, Reuters said. And, added Reuters, although each drug maker argued the benefits of its drugs and against banning LABAs, the advisory panel will vote next regarding the benefits and risks of each of the drugs.

Reuters noted that even if LABA approval for use in the treatment of asthma could face revocation, drugs such as Advair, Serevent, and Foradil could continue to be prescribed for patients suffering from chronic obstructive pulmonary disease (COPD). Meanwhile, AstraZeneca has applied to the FDA for approval of is asthma drug, Symbicort, to be used in the treatment of COPD.

Complications, Deaths Seen with Some Long-Acting Asthma Drugs

Fri, 05 Dec 2008 00:00:00 -0800

Some asthma drugs in a class known as long-acting beta agonists (LABA) can increase the risk of death and complications, a new Food & Drug Administration (FDA) analysis has found. The analysis looked at GlaxoSmithKline PLC's Serevent and Advair, Novartis AG's and Schering-Plough Corp.'s Foradil and AstraZeneca PLC's Symbicort.

The FDA analysis was prepared for an advisory committee meeting next week that is slated to discuss the safety of the drugs, The Wall Street Journal said. At the meeting, FDA advisors will consider whether LABAs should continue to be marketed for children and adults.

LABAs prevent the release of substances in the body that cause inflammation of airways in the lungs. In 2005, the FDA strengthened the warning labels for the asthma drugs to state that they should be reserved for patients who did not respond to other asthma therapies. The label changes came after a study found that patients taking Serevent where four times more likely to suffer an asthma-related death. Others showed that Serevent and Foradil increased asthma exacerbations and hospitalizations in both adults and children.

According to Reuters, the FDA's latest analysis found 2.8 more serious asthma events for every 1,000 asthma patients treated with a LABA. Children ages 4 to 11 "appeared to be at the greatest risk," FDA statisticians said. The risk is lower when the drugs are used together with a steroid to treat underlying inflammation deep inside the airways, Reuters said.

According to The Wall Street Journal, the analysis involved 110 trials and 60,954 patients. The bulk of the patients were from Serevent trials, with about 43,000 patients, the FDA said. The agency said there were 20 asthma-related deaths in the studies and of those, 16 were patients on Serevent and four were patients in the non-LABA group.

The analysis found that only one of the drugs, Advair - which combines an LABA and a steroid in one inhaler - does not appear to increase the risk of a serious event or death, the Journal said. However, Serevent had a significantly higher rate of serious complications than the others.

Asthma Drug Linked to Serious Adverse Events

Fri, 17 Oct 2008 00:00:00 -0700

The asthma drug formoterol, sold under the brand names Foradil (Novartis), Oxis (AstraZeneca), Atock (Astellas) and Perforomist, has been linked to an increased risk of non-fatal, serious adverse events, according to a new study. The study, conducted by Cochrane Researchers, found that people who took the drug daily for at least 12 weeks showed a significantly increased risk than those who took a placebo.

Formoterol is a long-acting beta2-agonist which is inhaled to help open the airways and last for 12 hours or more. Drugs like formoterol are used as "symptom controllers" to supplement preventive corticosteroid asthma therapy.

For their formoterol study, the Cochrane Researchers reviewed 22 studies involving 8,032 people diagnosed with asthma. In those studies that compared formoterol to a placebo, 16 patients per thousand taking formoterol suffered serious adverse effects, compared with only 10 per thousand in the group taking placebos. That translates to a 57 percent increase in non-fatal serious adverse events compared with placebo, the researchers said.

Serious adverse effects were most commonly asthma–related. The increase in adverse events was more marked in younger patients.

'It is possible that children are at a higher risk of suffering serious effects due to this drug, but we can't say for sure," Christopher Cates, B.M.B.Ch., of St. George's University of London, one of the authors of the study, said. "We would urge that all serious adverse events are more fully reported in medical journals so that we can make a better assessment of drug safety."

Three deaths occurred in patients taking formoterol compared with none in placebo patients, although the difference did not reach statistical significance.

"It was not possible to assess disease-specific mortality in view of the small number of deaths," the researchers said.

The same researchers released another study this past summer which found that the long-acting beta2-agonist, Serevent, also increased the likelihood of serious adverse events, including death. In a review of 26 double-blind randomized controlled trials, 45 of every 1,000 patients treated with Serevent had a serious adverse event, compared with 40 taking placebo.

Using data from two large surveillance studies, the researchers also found that regular Serevent use increased the risk of asthma-related mortality in patients who did not also use inhaled steroids. Also, the mortality from any cause was higher with Serevent than with placebo.

FDA Seeks Info on Serevent, Advair, Foradil As Part of Safety Review

Thu, 06 Mar 2008 00:00:00 -0800

Asthma drugs, including Serevent, Advair, Foradil, are the subject of a Food & Drug Administration (FDA) safety review. The FDA has requested information from the manufacturers of the asthma medications as part of an ongoing safety review of the drugs in children.

Serevent, Advair and Foradil are long-acting beta 2-adrenergic agonists that prevent the release of substances in the body that cause inflammation of airways in the lungs. In 2005, the FDA strengthened the warning labels for the asthma drugs to state that they should be reserved for patients who did not respond to other asthma therapies. The label changes came after a study found that patients taking Serevent where four times more likely to suffer an asthma-related death. Others showed that Serevent and Foradil increased asthma exacerbations and hospitalizations in both adults and children.

Asthma is a chronic disease marked by restricted breathing and wheezing, and often made worse by exercise, cigarette smoke and other factors. About 20 million people in the United States have asthma, according to the National Institutes of Health.

In November, prior to an FDA pediatric advisory panel meeting on the medications' use in children, the agency posted documents detailing nine patients under the age of 16 where injured while taking Serevent, and five died since the medication was approved for children in 2006. The FDA reviewers who posted the Serevent and Advair information did not identify whether the adverse events cited in the documents where unique to children, but they did write that Serevent might carry more risks than benefits for young users. The FDA report said that a study to assess the benefits and risks of Serevent and Advair might be needed, however, it conceded that would be difficult to find enough children to participate in such a clinical trial. Instead, the FDA report recommended that a more “formal” analysis of data regarding Serevent and Advair be conducted. The FDA's pediatric advisory panel ultimately recommended that the drugs' labels needed new language more specific to children.

The FDA said it plans to ask a panel of outside advisers to review the drugs' risks and benefits in adults and children in the fall or winter of 2008.

Researchers Say "Killer" Asthma Inhalers Should Be Recalled

Tue, 20 Jun 2006 00:00:00 -0700

Researchers from Cornell and Stanford universities have concluded three common asthma inhalers containing the drugs salmeterol or formoterol may be causing four out of five U.S. asthma-related deaths per year and should be taken off the market.

The researchers made their recommendation after concluding a search of medical literature.

They base these conclusions on a statistical analysis of 19 published trials involving 33,826 patients. This so-called meta-analysis found that patients who inhaled the long-acting beta-agonists salmeterol (trade names Serevent and Advair, both made by GlaxoSmithKline) or formoterol (trade name Foradil, made by Novartis Pharmaceuticals) were 3.5 times more likely to die from asthma and 2.5 times more likely to be hospitalized (whether or not death resulted), compared with those taking a placebo.

The reason, say the researchers, is because although these medications relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning.

Asthma death is relatively rare, 15 patients in the meta-analysis who were taking the beta-agonists died, compared with three in the placebo group, over a six-month period.

"In total, there are about 5,000 deaths a year due to asthma, whether or not a person is taking a long-acting beta-agonist," said Edwin Salpeter, the J.G. White Distinguished Professor of Physical Sciences Emeritus at Cornell, who led the statistical analysis in the study.

An eminent astrophysicist, Salpeter has more recently focused his attention on medical statistics.

"We can show that overall it is statistically significant that, compared to patients taking a placebo, these long-acting beta-agonists kill a lot of people," he said.

"These asthma deaths are generally in healthy young adults," said his daughter, Shelley Salpeter, the lead author of the paper appearing online and in the June 20 issue of Annals of Internal Medicine. She is a clinical professor of medicine at Stanford's School of Medicine and a physician at Santa Clara Valley Medical Center in San Jose, Calif.

"We estimate that approximately 4,000 out of the 5,000 asthma deaths that occur in the U.S. each year are actually caused by these long-acting beta-agonists, and we urge that these agents be taken off the market," she added.

Adding an anti-inflammatory drug to a long-acting beta-agonist adds little benefit, report the Salpeters.

Advair, for example, (the fourth bestselling drug in the world with $5.6 billion in annual sales), combines salmeterol with an anti-inflammatory drug to provide some protection against bronchial inflammation associated with beta-agonists. But hospitalizations still doubled for patients inhaling a long-acting beta-agonist combined with an anti-inflammatory drug compared with asthma patients taking a placebo and an anti-inflammatory drug by itself.

Of the 19 studies surveyed in the meta-analysis, the largest the Salmeterol Multicenter Asthma Research Trial with 26,000 participants reported a fourfold increased risk for asthma-related deaths and a twofold increase in life-threatening asthma events in patients using salmeterol.

If older people who also suffered from chronic obstructive pulmonary disease were removed from the analysis, the Salpeters report, salmeterol would be associated with a six times greater risk for asthma-related deaths.

The meta-analysis found that 53 of 3,083 patients inhaling beta-agonists were hospitalized for an asthma attack compared with 12 of 2,008 patients who received a placebo, meaning that there was one hospitalization for every 71 patients treated with a long-acting beta-agonist per year.

The Salpeters say that these two long-acting beta-agonists can result in death because tolerance to them develops over time.

"These agents can improve symptoms through bronchodilation at the same time as increasing underlying inflammation and bronchial hyper-responsiveness, thus worsening asthma control without any warning of increased symptoms," said Shelley Salpeter.

"It is particularly frightening that long-acting beta-agonists are detrimental, whether salmeterol or formoterol, whether taken alone or with anti-inflammatory drugs, both for children and for adults," said Ed Salpeter.

Asthma inhalers causing deaths - study

Tue, 20 Jun 2006 00:00:00 -0700

Three asthma inhalers with salmeterol or formoterol may cause 80 percent of U.S. asthma deaths annually, says a new study.

Because of the possible health risks, these products sold as GlaxoSmithKline's Serevent and Advair, and Novartis' Foradil should be recalled, said researchers at Cornell University and Stanford University.

"These asthma deaths are generally (occurring) in healthy young adults," said Stanford researcher Shelly Salpeter. "We estimate that approximately 4,000 of the 5,000 asthma deaths that occur in the U.S. each year are caused by these long-acting beta-agonists, and we urge that (they) be taken of the market."

The researchers conducted a statistical analysis of 19 published asthma trials involving 33,826 patients and found that people who used salmeterol-based asthma inhalers (Serevent and Advair) or inhalers containing formoterol (Foradil) were 3.5 times more likely to die from asthma.

The team also saw that these same patients were 2.5 times more likely to be hospitalized than asthma patients using a placebo inhaler.

Both drugs are in a drug class known as long-acting beta-agonists.

The researchers said that, although beta-agonists relieve bronchial spasm, they also promote bronchial inflammation and sensitivity without warning. Although Advair contains an anti-inflammatory to correct this problem, hospitalizations of patients taking Advair were still double those of people who took a placebo plus an anti-inflammatory, the team noted.

The study authors, whose paper appears in the June 20 issue of the Annals of Internal Medicine, noted that asthma death is relatively rare. Only 15 study patients who were taking the drugs died, compared to three in the placebo group over a six-month period, they said.

Common Asthma Inhalers Cause Up to 80% of Asthma-Related Deaths, Cornell and Stanford Researchers Assert

Fri, 09 Jun 2006 00:00:00 -0700

Three common asthma inhalers containing the drugs salmeterol or formoterol may be causing four out of five U.S. asthma-related deaths per year and should be taken off the market, researchers from Cornell and Stanford universities have concluded after a search of medical literature.

They base these conclusions on a statistical analysis of 19 published trials involving 33,826 patients. This so-called meta-analysis found that patients who inhaled the long-acting beta-agonists salmeterol (trade names Serevent and Advair, both made by GlaxoSmithKline) or formoterol (trade name Foradil, made by Novartis Pharmaceuticals) were 3.5 times more likely to die from asthma and 2.5 times more likely to be hospitalized (whether or not death resulted), compared with those taking a placebo.

The reason, say the researchers, is because although these medications relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning.

Nevertheless, asthma death is relatively rare 15 patients in the meta-analysis who were taking the beta-agonists died, compared with three in the placebo group, over a six-month period.

"In total, there are about 5,000 deaths a year due to asthma, whether or not a person is taking a long-acting beta-agonist," said Edwin Salpeter, the J.G. White Distinguished Professor of Physical Sciences Emeritus at Cornell, who led the statistical analysis in the study. An eminent astrophysicist, Salpeter has more recently focused his attention on medical statistics. "We can show that overall it is statistically significant that, compared to patients taking a placebo, these long-acting beta-agonists kill a lot of people," he said.

"These asthma deaths are generally in healthy young adults," said his daughter, Shelley Salpeter, the lead author of the paper appearing online and in the June 20 issue of Annals of Internal Medicine. She is a clinical professor of medicine at Stanford's School of Medicine and a physician at Santa Clara Valley Medical Center in San Jose, Calif.

"We estimate that approximately 4,000 out of the 5,000 asthma deaths that occur in the U.S. each year are actually caused by these long-acting beta-agonists, and we urge that these agents be taken off the market," she added.

Adding an anti-inflammatory drug to a long-acting beta-agonist adds little benefit, report the Salpeters. Advair, for example, (the fourth bestselling drug in the world with $5.6 billion in annual sales), combines salmeterol with an anti-inflammatory drug to provide some protection against bronchial inflammation associated with beta-agonists. But hospitalizations still doubled for patients inhaling a long-acting beta-agonist combined with an anti-inflammatory drug compared with asthma patients taking a placebo and an anti-inflammatory drug by itself.

Of the 19 studies surveyed in the meta-analysis, the largest the Salmeterol Multicenter Asthma Research Trial with 26,000 participants reported a fourfold increased risk for asthma-related deaths and a twofold increase in life-threatening asthma events in patients using salmeterol. If older people who also suffered from chronic obstructive pulmonary disease were removed from the analysis, the Salpeters report, salmeterol would be associated with a six times greater risk for asthma-related deaths.

The meta-analysis found that 53 of 3,083 patients inhaling beta-agonists were hospitalized for an asthma attack compared with 12 of 2,008 patients who received a placebo, meaning that there was one hospitalization for every 71 patients treated with a long-acting beta-agonist per year.

The Salpeters say that these two long-acting beta-agonists can result in death because tolerance to them develops over time.

"These agents can improve symptoms through bronchodilation at the same time as increasing underlying inflammation and bronchial hyper-responsiveness, thus worsening asthma control without any warning of increased symptoms," said Shelley Salpeter.

"It is particularly frightening that long-acting beta-agonists are detrimental, whether salmeterol or formoterol, whether taken alone or with anti-inflammatory drugs, both for children and for adults," said Ed Salpeter.

Co-authors of the study include Shelley Salpeter's son, Nicholas Buckley, a student at Sequoia High School in Redwood City, Calif., and Thomas Ormiston, a physician at Santa Clara Valley Medical Center in San Jose, Calif.

SOURCE: Cornell University

Advair, Other Asthma Drug Get Label Alerts

Mon, 06 Mar 2006 00:00:00 -0800

The asthma medication Advair and a related drug will bear stronger warnings of an increased risk of death associated with one of their ingredients.

The revised warnings apply to Advair and Serevent, Food and Drug Administration spokeswoman Laura Alvey said Monday. Advair is GlaxoSmithKline's best-selling product, and Serevent is another of the British company's drugs.

The updated versions of the "black-box" warnings on both drugs caution that salmeterol, one of the active ingredients in Advair and the active ingredient in Serevent, may increase the risk of asthma-related death. Black-box warnings are the most severe warnings the FDA can require of prescription drugs.

Advair should be used only by patients when other asthma drugs, such as low- to medium-dose inhaled corticosteroids, don't work or if their asthma is severe enough to merit use of two medications, the revised warning says.

As for Serevent, it should only be used as an additional medication when the low- to medium-dose inhaled corticosteroids aren't sufficient or, again, if the asthma is serious enough to merit use of two drugs.

The FDA in November asked that the labels be updated for the two drugs, along with a third, Foradil.

Foradil's manufacturer, Novartis, remains in talks with the FDA and no final decision has been reached, said Julie Lux, a spokeswoman for Schering-Plough Corp., which markets Foradil in the United States.

GlaxoSmithKline said in a statement that it was pleased to reach an agreement with the FDA on the label changes to its two drugs.

"The new product labels communicate the benefit-risk profile of Serevent and Advair and help guide physicians in making appropriate prescribing decisions," the company said. In November, however, it maintained that the drugs already came with sufficient warning. The company reported in February that sales of Advair, sold as Seretide in the United Kingdom, rose 22 percent last year to $5.2 billion.

The FDA last Friday released new medications guides for patients using the two GlaxoSmithKline drugs. The letters urge asthmatics using the drugs to talk to their doctors about the relative risks and benefits of the medicines.

The agency said a large U.S. study found that more people using the asthma drugs died from their asthma compared with those taking dummy medication. The number of asthma deaths in the study was small, however: just 13 out of 13,176 patients.

The drugs help with long-term control and prevention of asthma symptoms like wheezing and shortness of breath. They help the muscles around the airways in the lungs stay relaxed.

Serevent, Advair, and Foradil Linked to Risk of Severe Asthma Exacerbations, Death

Fri, 18 Nov 2005 00:00:00 -0800

The U.S. Food and Drug Administration (FDA) has warned healthcare professionals regarding the increased risk of severe asthma episodes and death associated with use of inhalation powders containing long-acting beta 2-adrenergic agonists (LABA) such as salmeterol xinafoate and formoterol fumarate.

Inhalation powders included in the warning include salmeterol (Serevent Diskus, made by GlaxoSmithKline), salmeterol combined with fluticasone propionate (Advair Diskus, made by GlaxoSmithKline), and formoterol (Foradil Aerolizer, made by Novartis Pharmaceuticals Corp.).

Patients receiving these medications should be advised to seek medical attention immediately if their asthma worsens, according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting system.

The warning was based on data from a 28-week clinical trial (Salmeterol Multi-center Asthma Research Trial [SMART]) in 26,355 patients, showing that addition of salmeterol to usual asthma therapy was associated with an increased risk of fatal asthma events compared with placebo (13 vs 3 deaths; 0.10% vs 0.02%). These results led to early discontinuation of the study.

Although post-hoc subpopulation analyses suggested that the relative risk (RR) of death was similar among whites (RR, 5.82; 95% confidence interval [CI], 0.70 - 48.27) and African Americans (RR, 7.26; 95% CI, 0.89 - 58.94), incidence rates were higher among African Americans.

The results from SMART were similar to those of the Salmeterol Nationwide Surveillance (SNS) study in 25,180 patients, showing the incidence of respiratory and asthma-related death to be numerically (though not statistically) greater with addition of salmeterol rather than albuterol to usual asthma therapy (12 vs 2 deaths).

Although no studies have been adequate to determine whether formoterol is also associated with an increased rate or relative risk of asthma-related death, smaller studies have linked its use to an increased incidence of serious asthma exacerbations compared with albuterol and placebo.

Healthcare professionals with asthma patients receiving these medications should be aware that LABAs are not intended as first-line therapy and should be reserved for use in those who have demonstrated an inadequate response to other asthma-controller medications such as inhaled corticosteroids.

Current guidelines from the National Heart, Lung, and Blood Institute and World Health Organization recommend inhaled corticosteroids as the first step in controller therapy, with LABAs as optional add-on therapy if low- to medium-dose inhaled corticosteroids provide inadequate relief.
The FDA notes that the warning applies to use of LABAs for the long-term control and prevention of asthma symptoms. Information is not available to determine the relevance of these findings in patients using LABAs for the prevention of exercise-induced bronchospasm or long-term control of bronchospasm due to chronic obstructive pulmonary disease.

Adverse events related to the use of long-acting beta 2-agonists should be reported to the FDA's MedWatch program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

Safety Information About A Class of Asthma Drugs Known As Long-Acting Beta-2 Agonists

Tue, 04 Oct 2005 00:00:00 -0700

Health Canada is advising Canadians of the possible increased risks of asthma-related deaths associated with the use of a class of asthma drugs known as long-acting beta-2 agonists.

Further, Health Canada is reminding Canadians of the recommended uses of long-acting beta-2 agonists.

The asthma medications are salmeterol, which is sold under the brand name Serevent; formoterol, sold as Foradil and Oxeze; as well as two combination products containing salmeterol or formoterol in addition to an inhaled corticosteroid. The combination product with salmeterol is sold as Advair, while the formoterol product is sold as Symbicort.

This advisory is based on a Health Canada analysis of findings from an asthma research trial conducted by GlaxoSmithKline, known as the Salmeterol Multi-center Asthma Research Trial, or SMART. The SMART study began in 1996 at the request of the U.S. Food and Drug Administration (FDA), due to increasing safety concerns about regular long-term use of salmeterol in the treatment of asthma. The study of approximately 30,000 patients was prematurely halted in January 2003 after an interim analysis suggested an increased risk of asthma-related death in patients who use Serevent (as compared to a placebo) in addition to their usual asthma therapy. The SMART study data was reviewed by an FDA advisory committee in July 2005 that looked at the safety of these asthma medications. The committee voted unanimously to keep this class of drugs on the market.

Although not conclusive, the SMART study suggests that risks may be higher in African-American patients and in those patients who were not being treated with inhaled corticosteroids at the start of the study. Corticosteroids are a family of drugs with anti-inflammatory effects that are used in asthma treatment, and they are most commonly used in the form of a powder inhaled directly or can be given orally in more severe cases.

Health Canada monitored the FDA advisory committee in July, which noted that increased risks with salmeterol may also apply to other long-acting beta-2 agonist medications such as formoterol, although data to confirm this is not yet available.

Health Canada recommends that:

Salmeterol and formoterol can only be used with an appropriate dose of inhaled corticosteroid as determined by a physician.

Long-acting beta-2 agonists are not a substitute for inhaled or oral corticosteroids.
Serevent, Foradil or Advair should never be used to treat acute or sudden onset of asthma symptoms and attacks.
Symbicort is not indicated for the treatment of sudden asthma symptoms and attacks.

Oxeze may be used to treat acute, or the sudden onset of asthma symptoms, in patients 12 years and older.
Medical attention should be sought if a patient's use of asthma medications becomes less effective, or if more inhalations than usual are required.

Patients must not stop or reduce their asthma therapy without first consulting their prescribing physician. Abruptly stopping medications may result in deteriorating asthma control, which can be life-threatening.
Patients with asthma who have any questions about their current prescription or treatment should contact their physician or pharmacist directly.

The prescribing information for Serevent and Advair has been updated. Health Canada is engaged in an ongoing review of these products, and is in the process of reviewing the safety data for the other long-acting beta-2 agonists. Further action may be taken if necessary.

Health Canada has requested that manufacturers of these medications inform physicians of the SMART study findings and of the outcome of the FDA advisory committee meeting. The FDA panel only reviewed data relating to Serevent (salmeterol) and Foradil (formoterol).

Long-acting beta-2 agonists are prescribed as regular treatment to prevent asthma symptoms such as wheezing, shortness of breath and cough. Serevent and Advair are manufactured by GlaxoSmithKline. Foradil is manufactured by Novartis, and Oxeze and Symbicort are manufactured by AstraZeneca.

FDA Orders "Black Box" Warning for Asthma Drugs

Thu, 14 Jul 2005 00:00:00 -0700

The US Food and Drug Administration has cleared asthma drugs Advair and Serevent, allowing them to stay on the market as long as warning labels clearly alert patients to potential risks.

Made by GlaxoSmithKline, the medications contain salmeterol, a bronchodilator known as a beta2-agonist. It works by relaxing the bronchial muscles, thereby improving air flow for many of the 15 million asthma sufferers in the U.S.

Regulators became alarmed when Glaxo reported that it had to stop tests of the drug when about 50 out of 26,000 patients being studied suffered more severe asthma attacks. A few died.

After a review by its panel of experts, the FDA voted 12-0 to keep the drugs on the market while adding a "black box" warning, the most extreme warning that can be put on drugs.

The tests were launched in 1996 at the behest of the FDA to address specific questions about Serevent and Advair. In 2003, the trials were stopped after 50 people experienced serious, life-threatening episodes or died, compared with 36 episodes in patients who had been given a placebo.

One statistic that initially raised concerns was that African-Americans in the study appeared to have a higher rate of death. Twenty black people who had receive the drug died, compared with five who were taking the placebo.

But doctors involved in the study and other researchers agreed that the statistic was misleading and did not indicate that blacks were at higher risk of dying from taking the drugs. FDA panelists stressed that the higher death rate in the test was a fluke and that it would be irresponsible to mislead blacks into turning from medication that could prolong their lives.

Asthma is a dangerous disease, especially when it is untreated or under-treated. No one now taking prescribed medications should stop taking them without consulting their physician. It can be dangerous to suddenly stop taking prescribed medications.

Sales of Servent and Advair, marketed as Seretide in Europe, topped $4 billion last year. Novartis' asthma remedy, Foradil, which was also reviewed, brought in only $320 million.

Salmeterol Warning Cites Risk of Asthma Deaths

Wed, 01 Oct 2003 00:00:00 -0700

The labels of three GlaxoSmithKline asthma products containing salmeterol now have boxed warnings citing a "small but significant increase in asthma-related deaths," based on recommendations from the Food and Drug Administration.

The interim results of a study of approximately 29,000 asthma patients in the Salmeterol Multi-Center Asthma Research Trial (SMART) showed more asthma-related deaths and life-threatening asthmatic episodes among African American patients taking salmeterol than among those taking a placebo.

The products with label changes are Serevent Inhalation Aerosol (salmeterol xinafoate), Serevent Diskus (salmeterol xinafoate inhalation powder), and Advair Diskus (fluticasone propionate and salmeterol inhalation powder). Serevent Diskus is approved for treatment of asthma in patients aged 4 years and older, while both Serevent Inhalation Aerosol and Advair Diskus are approved for patients aged 12 years and older.

The "Dear Healthcare Professional" letter included with the products states that patients currently taking these medications should not stop suddenly this may lead to life-threatening asthmatic episodes due to uncontrolled asthma. In addition, the letter reminds physicians that patients taking salmeterol as their only asthma therapy should add an inhaled corticosteroid to their treatment regimens.

However, the warning implies a much broader problem than exists, Dr. Harold Nelson, professor of medicine at the National Jewish Medical and Research Center, Denver, told this newspaper. The adverse outcomes occurred in patients who were not only African American, but who were not taking inhaled corticosteroids. Those taking inhaled corticosteroids concurrently with salmeterol had no adverse effects, regardless of ethnicity.

In a 28-week safety study, asthma patients aged 12 years and older were given either 42 [micro]g of salmeterol or a placebo twice daily. Although the study was meant to include approximately 60,000 patients, it was stopped at the halfway point due to evidence of increased risk of asthma-related deaths among patients who received salmeterol: 13 deaths among 13,174 patients, compared with 4 asthma-related deaths among 13,179 patients who received placebo. Approximately 17% of the study subjects were African American.

The SMART study did not include outcome analyses based on demographic traits, but a later subgroup analysis showed a statistically significant increase in the number of asthma-related deaths among African American patients who received salmeterol compared with those who received placebo (eight vs. one). In addition, a weakness of the SMART study is that the only information about concomitant medication is the form that patients filled out at the beginning of the study, Dr. Nelson noted.

However, the FDA maintains that the benefits of salmeterol outweigh the risks when patients with asthma and chronic obstructive pulmonary disease use the medication properly and that includes taking inhaled corticosteroids concomitantly.

Foradil Advair Serevent Asthma Death Injury Lawyer

Wed, 01 Oct 2003 00:00:00 -0700

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Injured by Foradil?

Foradil received FDA approval on February 16, 2001 to treat asthma. The FDA’s Pulmonary-Allergy Drugs Advisory Committee said on July 13, 2005 that Foradil, manufactured by Novartis; (Generic: Formoterol), should add a “black box” warning stating safety issues associated with GlaxoSmithKline’s Serevent, a similar drug in the class.

The committee voted 12 to zero, with one abstention, that labeling for Foradil (formoterol) should include a warning citing asthma-related deaths seen with Serevent (Salmeterol). Labeling for Serevent, and combination product Advair (Salmeterol/Fluticasone), was modified in September 2004 to incorporate statistics from the SMART study. The study illustrated a 1.71 relative risk of asthma death or life-threatening experience with use of Salmeterol compared to placebo. The drugs added a boxed warning in August 2003 based on the preliminary results of the study.

The committee members felt that adding a warning to Foradil would alert physicians and patients that the drug might be no safer than Salmeterol products. The burden should be on Novartis to show that Formoterol has a different mechanistic or safety profile from Salmeterol, committee members said. The committee members also recommended the dissemination of more physician and patient information on the risks of Salmeterol products, including a patient medication guide.

Foradil Label Update
The FDA announced on May 16, 2006 that the product label for Foradil has been updated with a warning that the drug might increase the chance of severe asthma attacks that can result in death.

If you or a loved one took Foradil and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.