Cuban scientists discover new drugs for fighting heart diseases, parasites
Cuban researchers have discovered substances that can reverse the side effects of drugs used to fight heart diseases and parasites, the country's Juventud Rebelde newspaper reported Tuesday.
The chemicals were derived from tiadiazines, based on their potential anti-parasite properties and the diversification of heterocyclical systems with pharmaceutical properties, the newspaper quoted Hortensia Rodriguez, head of Havana University's Organic Synthesis Laboratory, as saying.
After studying new agents which could be more effective against dangerous parasites, the researchers then sought compounds with novel molecular structures, using methods with a minimal environmental impact, the newspaper said.
Heart diseases and acute parasitic infections are among the world's most serious diseases.
Showing posts with label drug. Show all posts
Showing posts with label drug. Show all posts
Wednesday, January 9, 2008
Study challenges drug's role in autism
Study challenges drug's role in autism
The use of mercury-based preservative thimerosal may not be linked with autism as previously thought, according to a new study.
The prevalence of autism in California children continued to rise after many vaccine manufacturers started to remove the mercury-based preservative thimerosal in 1999, suggesting that the chemical was not a primary cause of the disorder, according to the study published in the January issue of the Archives of General Psychiatry.
The analysis found that from 2004 to 2007, when exposure to thimerosal dropped significantly for 3- to 5-year-olds, the rate continued to increase in that group from 3.0 to 4.1 per 1,000 children, according to the study.
"If mercury exposure in vaccines was a major cause of autism, then the number of ... affected kids should have diminished once they were no longer exposed to thimerosal," said Dr. Robert Schechter, lead author of the study and a medical officer at the state Department of Public Health. "That is not what we found."
The study is the latest in a series that has investigated the connection between thimerosal and autism. The majority have found no association.
The latest study was based on data from the California Department of Developmental Services, which provides services to about 36,000 people with autism and has one of the country's best reporting systems.
The researchers looked at all reported cases in the state of California starting with children born in 1989. They found the number of cases per 1,000 children has been steadily increasing from that point to March 2007, the end point of the study.
Steve M. Edelson, an experimental psychologist who is director of the Autism Research Institute, a nonprofit organization in San Diego of California, said the study, along with evidence from previous research, argued against thimerosal as the major culprit in autism.
But, he added, it still does not rule out all blame. Edelson said such large-scale analysis could overlook smaller groups of children, who for whatever reasons have a particular vulnerability to mercury. He said more solid evidence can only come from laboratory studies, such as postmortem analyses of the brains of autistic children.
The use of mercury-based preservative thimerosal may not be linked with autism as previously thought, according to a new study.
The prevalence of autism in California children continued to rise after many vaccine manufacturers started to remove the mercury-based preservative thimerosal in 1999, suggesting that the chemical was not a primary cause of the disorder, according to the study published in the January issue of the Archives of General Psychiatry.
The analysis found that from 2004 to 2007, when exposure to thimerosal dropped significantly for 3- to 5-year-olds, the rate continued to increase in that group from 3.0 to 4.1 per 1,000 children, according to the study.
"If mercury exposure in vaccines was a major cause of autism, then the number of ... affected kids should have diminished once they were no longer exposed to thimerosal," said Dr. Robert Schechter, lead author of the study and a medical officer at the state Department of Public Health. "That is not what we found."
The study is the latest in a series that has investigated the connection between thimerosal and autism. The majority have found no association.
The latest study was based on data from the California Department of Developmental Services, which provides services to about 36,000 people with autism and has one of the country's best reporting systems.
The researchers looked at all reported cases in the state of California starting with children born in 1989. They found the number of cases per 1,000 children has been steadily increasing from that point to March 2007, the end point of the study.
Steve M. Edelson, an experimental psychologist who is director of the Autism Research Institute, a nonprofit organization in San Diego of California, said the study, along with evidence from previous research, argued against thimerosal as the major culprit in autism.
But, he added, it still does not rule out all blame. Edelson said such large-scale analysis could overlook smaller groups of children, who for whatever reasons have a particular vulnerability to mercury. He said more solid evidence can only come from laboratory studies, such as postmortem analyses of the brains of autistic children.
Tuesday, January 1, 2008
Drug Helps Fight Late-Stage Colon Cancer in Some Patients
Drug Helps Fight Late-Stage Colon Cancer in Some Patients
WEDNESDAY, Nov. 14 (HealthDay News) -- A highly targeted biologicdrug called cetuximab (Erbitux) is the first to extend the survival ofpatients with advanced colon cancer who have otherwise proved resistant toconventional chemotherapy, Canadian researchers confirmed.
But the drug, which costs $12,000 a month in the United States, appearsto be effective in only about one-third of colon tumors, based on theirspecific gene profile, experts added.
"That's a significant number, but it still leaves a large proportion[of patients] who aren't benefiting," noted lead researcher Dr. DerekJonker, assistant professor of medicine at the University of Ottawa and amedical oncologist at the Ottawa Hospital.
Nevertheless, the success of any new drug is welcome, he added.
"Until now, no anticancer therapy had demonstrated an improvement insurvival in patients for whom chemotherapy was no longer effective, andfor whom supportive care was the only available treatment," Jonker said."So, cetuximab provides new hope for these patients."
The findings were reported in the Nov. 15 issue of the New EnglandJournal of Medicine. The study was funded by the National CancerInstitute of Canada, as well as ImClone Systems and Bristol-Myers Squibb,the two companies that developed the drug.
Colorectal cancer is the third most common kind of cancer and the thirdleading cause of cancer death in the United States. As Jonker explained,most patients are treated with either surgery or conventionalchemotherapy, which typically targets cellular DNA.
Unfortunately, almost all patients with advanced or metastasized coloncancer will develop resistance to standard chemotherapy drugs, hesaid.
"However, now we have a new class of drugs known as the biologicallytargeted therapies, such as cetuximab, and these drugs are targeted todifferent aspects of the tumor biology," Jonker explained. "Many of themare targeted at receptors or signals that trigger a cancer cell togrow."
In the case of cetuximab, the drug's target is the epidermal growthfactor receptor (EGFR), which is found in especially high concentrationson colon cancer cells. Because biologic drugs are finely targeted toaffect cancer cells and not healthy cells, they typically have fewer sideeffects than standard chemotherapy.
In 2004, the U.S. Food and Drug Administration granted cetuximabconditional approval for use in patients with late-stage,chemotherapy-resistant colon cancer. At the time, the agency stated thatfull approval hinged on the outcome of the Canadian trial.
In October, and based on the new findings, the agency followed throughand gave the drug its full approval for this new indication.
In the trial, Jonker's team administered individualized doses ofcetuximab to 287 colon cancer patients treated between late 2003 andAugust 2005. All of the patients had proven resistant to standardchemotherapy. Another 285 patients received supportive/palliative careonly -- the usual option for patients in this situation.
Compared to those who didn't receive the drug, overall survival forpatients receiving cetuximab improved by 23 percent, while survivalwithout any sign of disease progression rose by 32 percent, the researchteam reported.
The incidence of side effects -- including skin rash -- was 78.5percent in the cetuximab group versus about 59 percent for the controlgroup.
One key point, however, was that increases in survival were found onlyamong the 31.4 percent of patients who actually responded to cetuximab,meaning that their cancer stopped growing.
That's probably due to the fact that cetuximab (as well as a relateddrug, panitumumab) only works against a specific subtype of colon cancercell -- those carrying an unmutated version of a particular gene calledKRAS.
"Mutated KRAS almost guarantees no benefit" from cetuximab, said oneexpert, Dr. Axel Grothey, a professor of oncology and chairman of thecolorectal cancer group at the Mayo Clinic, in Rochester, Minn.
For that reason, he said, pre-treatment gene testing may prove crucialto decisions as to whether a particular patient receives cetuximab ornot.
Because it is so expensive -- the costliest drug used today againstcolon cancer -- and because it can induce side effects, "I would likecetuximab to be used in a more individualized way," Grothey said.
He said that most cancer centers, including the Mayo Clinic, do not yethave technologies in place to test tumors for KRAS, but many are lookinginto it.
Jonker agreed that, ideally, KRAS testing and the use of cetuximabwould go hand-in-hand. That way, he said, "We wouldn't have to put[patients] through treatment, and we wouldn't have to suffer the cost oftreatment for people who may not even respond to the drug."
Studies are already under way to see if adding cetuximab to othertherapies will boost survival even further, Jonker said. "The future ofcetuximab is likely to be in combination with chemotherapy or otherbiologically targeted therapies, where the benefits of cetuximab might befurther enhanced," he said.
The drug might also work better if given earlier in the diseaseprocess, before patients have developed resistance to chemotherapy.
In any case, the Canadian trial does give colon cancer patients somenew reason for hope, Grothey said. "We need this drug," he said, "and weprobably need it even earlier."
WEDNESDAY, Nov. 14 (HealthDay News) -- A highly targeted biologicdrug called cetuximab (Erbitux) is the first to extend the survival ofpatients with advanced colon cancer who have otherwise proved resistant toconventional chemotherapy, Canadian researchers confirmed.
But the drug, which costs $12,000 a month in the United States, appearsto be effective in only about one-third of colon tumors, based on theirspecific gene profile, experts added.
"That's a significant number, but it still leaves a large proportion[of patients] who aren't benefiting," noted lead researcher Dr. DerekJonker, assistant professor of medicine at the University of Ottawa and amedical oncologist at the Ottawa Hospital.
Nevertheless, the success of any new drug is welcome, he added.
"Until now, no anticancer therapy had demonstrated an improvement insurvival in patients for whom chemotherapy was no longer effective, andfor whom supportive care was the only available treatment," Jonker said."So, cetuximab provides new hope for these patients."
The findings were reported in the Nov. 15 issue of the New EnglandJournal of Medicine. The study was funded by the National CancerInstitute of Canada, as well as ImClone Systems and Bristol-Myers Squibb,the two companies that developed the drug.
Colorectal cancer is the third most common kind of cancer and the thirdleading cause of cancer death in the United States. As Jonker explained,most patients are treated with either surgery or conventionalchemotherapy, which typically targets cellular DNA.
Unfortunately, almost all patients with advanced or metastasized coloncancer will develop resistance to standard chemotherapy drugs, hesaid.
"However, now we have a new class of drugs known as the biologicallytargeted therapies, such as cetuximab, and these drugs are targeted todifferent aspects of the tumor biology," Jonker explained. "Many of themare targeted at receptors or signals that trigger a cancer cell togrow."
In the case of cetuximab, the drug's target is the epidermal growthfactor receptor (EGFR), which is found in especially high concentrationson colon cancer cells. Because biologic drugs are finely targeted toaffect cancer cells and not healthy cells, they typically have fewer sideeffects than standard chemotherapy.
In 2004, the U.S. Food and Drug Administration granted cetuximabconditional approval for use in patients with late-stage,chemotherapy-resistant colon cancer. At the time, the agency stated thatfull approval hinged on the outcome of the Canadian trial.
In October, and based on the new findings, the agency followed throughand gave the drug its full approval for this new indication.
In the trial, Jonker's team administered individualized doses ofcetuximab to 287 colon cancer patients treated between late 2003 andAugust 2005. All of the patients had proven resistant to standardchemotherapy. Another 285 patients received supportive/palliative careonly -- the usual option for patients in this situation.
Compared to those who didn't receive the drug, overall survival forpatients receiving cetuximab improved by 23 percent, while survivalwithout any sign of disease progression rose by 32 percent, the researchteam reported.
The incidence of side effects -- including skin rash -- was 78.5percent in the cetuximab group versus about 59 percent for the controlgroup.
One key point, however, was that increases in survival were found onlyamong the 31.4 percent of patients who actually responded to cetuximab,meaning that their cancer stopped growing.
That's probably due to the fact that cetuximab (as well as a relateddrug, panitumumab) only works against a specific subtype of colon cancercell -- those carrying an unmutated version of a particular gene calledKRAS.
"Mutated KRAS almost guarantees no benefit" from cetuximab, said oneexpert, Dr. Axel Grothey, a professor of oncology and chairman of thecolorectal cancer group at the Mayo Clinic, in Rochester, Minn.
For that reason, he said, pre-treatment gene testing may prove crucialto decisions as to whether a particular patient receives cetuximab ornot.
Because it is so expensive -- the costliest drug used today againstcolon cancer -- and because it can induce side effects, "I would likecetuximab to be used in a more individualized way," Grothey said.
He said that most cancer centers, including the Mayo Clinic, do not yethave technologies in place to test tumors for KRAS, but many are lookinginto it.
Jonker agreed that, ideally, KRAS testing and the use of cetuximabwould go hand-in-hand. That way, he said, "We wouldn't have to put[patients] through treatment, and we wouldn't have to suffer the cost oftreatment for people who may not even respond to the drug."
Studies are already under way to see if adding cetuximab to othertherapies will boost survival even further, Jonker said. "The future ofcetuximab is likely to be in combination with chemotherapy or otherbiologically targeted therapies, where the benefits of cetuximab might befurther enhanced," he said.
The drug might also work better if given earlier in the diseaseprocess, before patients have developed resistance to chemotherapy.
In any case, the Canadian trial does give colon cancer patients somenew reason for hope, Grothey said. "We need this drug," he said, "and weprobably need it even earlier."
New Drug Fights Medication-Linked Bone Loss
New Drug Fights Medication-Linked Bone Loss
WEDNESDAY, Nov. 14 (HealthDay News) -- An osteoporosis drug hasproven superior to standard therapy at slowing bone loss caused by asthmatreatment, researchers say.
Glucocorticoid medicines such as prednisone are often given to treatasthma, autoimmune disorders, skin allergies and other conditions,researchers note. But the drugs can also cause osteoporosis.
The drug, an anabolic agent called teriparatide, probably will be thepreferable treatment "for patients who have particularly bad disease tostart with or are on glucocorticoids for a long time," said Dr. Kenneth G.Saag, professor of medicine and epidemiology at the University of Alabamaat Birmingham.
The study, which was funded by teriparatide's maker, Eli Lilly &Co., is published in the Nov. 15 issue of the New England Journal ofMedicine.
One million Americans are taking glucocorticoids for one condition oranother, Saag said, and many are at higher risk of fractures, because themedications weaken their bones. Current treatment for medication-linkedosteoporosis centers on use of bisphosphonates, medications designed toprevent bone breakdown.
The 18-month trial included 428 men and women with drug-causedosteoporosis who had been taking glucocorticoids for at least threemonths. Half were assigned to take alendronate, a bisphosphonate, whilethe other half took teriparatide.
After three months, the increase in bone density at the lumbar (lower)spine was double for those taking teriparatide -- an average 7.2 percentrise versus 3.4 percent in the alendronate group. The teriparatide groupalso experienced fewer fractures of the vertebral bones compared withthose on the bisphosphonate.
But teriparatide's much higher cost will limit its use, Saag said. "Useof therapy is driven by insurance as well as by appropriate bone densityand fracture rate," he said. "We would like to be able to single out thosepatients whose minimal bone density puts them at higher risk forfracture," Saag said. "Those patients are the ones we want to target moreaggressively."
That group would include 30 percent to 50 percent of those withdrug-caused osteoporosis, he said. The U.S. Food and Drug Administrationalready has approved use of teriparatide for the treatment of osteoporosisin postmenopausal women at high risk for fracture and to increase bonemass in men at high risk of fracture with primary or hypogonadalosteoporosis.
The anabolic agent is a better treatment, because bisphosphonates donot actually promote bone growth, added Dr. Robert R. Recker, professor ofmedicine at Creighton University and a member of the Osteoporosis ResearchCenter there. Rather, they prevent bone destruction by natural processessuch as apoptosis (natural cell death), he said
"There is a greater need for a bone-forming agent, one that interfereswith the apoptosis of bone cells," Recker said. "The condition is not somuch a low bone mass disease but a disease of bone cells that results intoo much remodeling. Bisphosphonates lower remodeling. [Teriparatide]increases new bone formation."
But longer-term studies are still needed to assess teriparatide'seffects over prolonged periods, Recker said.
"Not one study has gone long enough to see if you get more benefits byusing it for a long time," he said. "It may be good for 24 months. Thatremains to be seen."
WEDNESDAY, Nov. 14 (HealthDay News) -- An osteoporosis drug hasproven superior to standard therapy at slowing bone loss caused by asthmatreatment, researchers say.
Glucocorticoid medicines such as prednisone are often given to treatasthma, autoimmune disorders, skin allergies and other conditions,researchers note. But the drugs can also cause osteoporosis.
The drug, an anabolic agent called teriparatide, probably will be thepreferable treatment "for patients who have particularly bad disease tostart with or are on glucocorticoids for a long time," said Dr. Kenneth G.Saag, professor of medicine and epidemiology at the University of Alabamaat Birmingham.
The study, which was funded by teriparatide's maker, Eli Lilly &Co., is published in the Nov. 15 issue of the New England Journal ofMedicine.
One million Americans are taking glucocorticoids for one condition oranother, Saag said, and many are at higher risk of fractures, because themedications weaken their bones. Current treatment for medication-linkedosteoporosis centers on use of bisphosphonates, medications designed toprevent bone breakdown.
The 18-month trial included 428 men and women with drug-causedosteoporosis who had been taking glucocorticoids for at least threemonths. Half were assigned to take alendronate, a bisphosphonate, whilethe other half took teriparatide.
After three months, the increase in bone density at the lumbar (lower)spine was double for those taking teriparatide -- an average 7.2 percentrise versus 3.4 percent in the alendronate group. The teriparatide groupalso experienced fewer fractures of the vertebral bones compared withthose on the bisphosphonate.
But teriparatide's much higher cost will limit its use, Saag said. "Useof therapy is driven by insurance as well as by appropriate bone densityand fracture rate," he said. "We would like to be able to single out thosepatients whose minimal bone density puts them at higher risk forfracture," Saag said. "Those patients are the ones we want to target moreaggressively."
That group would include 30 percent to 50 percent of those withdrug-caused osteoporosis, he said. The U.S. Food and Drug Administrationalready has approved use of teriparatide for the treatment of osteoporosisin postmenopausal women at high risk for fracture and to increase bonemass in men at high risk of fracture with primary or hypogonadalosteoporosis.
The anabolic agent is a better treatment, because bisphosphonates donot actually promote bone growth, added Dr. Robert R. Recker, professor ofmedicine at Creighton University and a member of the Osteoporosis ResearchCenter there. Rather, they prevent bone destruction by natural processessuch as apoptosis (natural cell death), he said
"There is a greater need for a bone-forming agent, one that interfereswith the apoptosis of bone cells," Recker said. "The condition is not somuch a low bone mass disease but a disease of bone cells that results intoo much remodeling. Bisphosphonates lower remodeling. [Teriparatide]increases new bone formation."
But longer-term studies are still needed to assess teriparatide'seffects over prolonged periods, Recker said.
"Not one study has gone long enough to see if you get more benefits byusing it for a long time," he said. "It may be good for 24 months. Thatremains to be seen."
Lancet, BMJ studies sound concern over anti-obesity drug rimonabant
Lancet, BMJ studies sound concern over anti-obesity drug rimonabant
A woman stands outside a sandwich shop. Two overviews of trials of weight-loss drugs have added to concerns that the obesity treatment rimonabant may boost the risk of depression and anxiety.(AFP/File/Paul Ellis)PARIS (AFP) - Two overviews of trials of weight-loss drugs have added to concerns that the obesity treatment rimonabant may boost the risk of depression and anxiety.
The papers, published in Saturday's issue of The Lancet and online Friday by the British Medical Journal (BMJ), follow a decision in June by an advisory panel to the US Food and Drug Administration (FDA) that voted against marketing rimonabant in the United States on safety grounds.
Doctors led by Arne Astrup, a professor at the Faculty of Life Sciences at the University of Copenhagen, analysed four trials in which 4,105 patents were either given a 20mg daily dose of rimonabant or a dummy lookalike pill called a placebo.
Over one year, patients on rimonabant realised a weight loss that was 4.7 kilos (10.3 pounds) higher than counterparts in the placebo group.
But they were also 40 percent likelier to experience "adverse" or "serious adverse" events, according to Astrup's study, which appears in The Lancet.
Patients on rimonabant were two and a half times likelier to stop taking the drug because of depression than those on placebo, and three times likelier to discontinue the treatment because of anxiety.
The findings are significant because individuals with a history of depression -- a phenomenon common among the severely obese -- were specifically excluded from the trial, say the authors.
"We recommend increased alertness by physicians to these potentially severe psychiatric reactions," the Lancet paper says.
Meanwhile, a study published online Friday by the British Medical Journal (BMJ) said that rimonabant and two other anti-obesity drugs, orlistat and sibutramine, were of only limited effect in terms of weight loss over the long term.
Canadian researchers reviewed data from 30 trials in which obese volunteers -- average weight 100 kilos (220 pounds) -- took either anti-obesity drugs or a placebo for a year or more.
The three drugs reduced weight by less than five kilos (11 pounds), equivalent to a loss of less than five percent of total body weight.
The three drugs had various beneficial side effects but all had adverse effects, including, in rimonabant's case, an increase in depression and anxiety, they said.
The authors noted that no trials examined rates of death and disease as a result of taking anti-obesity pills and called for trials to looking into this aspect.
In June, all 14 experts on the FDA's Advisory Committee said rimonabant, which French maker Sanofi-Aventis had hoped would become a blockbuster drug under the brand name of Zimulti, voted against authorising the drug after they heard evidence that it was linked with an increased risk of suicide.
The European Union has approved rimonabant, locally marketed as Acomplia, as a support for diet and exercise for obese patients who have Type 2 diabetes and cardiovascular problems associated with obesity.
However, labelling of the drug has been stepped up to warn against prescribing it to European patients with depression or those taking anti-depressants.
A trial among 1,047 volunteers, published in The Lancet in October 2006, found ribonant improved control over blood glucose and blood fats among people with Type 2 diabetes.
The drug was "generally well tolerated," the study said. Among those volunteers who dropped out of the trial, depression, nausea and dizziness were the most cited reasons among the rimonabant group.Rimonabant blocks endocannabinoid receptors in the brain that cause hunger.Global sales of anti-obesity drugs reached 1.2 billion dollars in 2005, the BMJ said.
A woman stands outside a sandwich shop. Two overviews of trials of weight-loss drugs have added to concerns that the obesity treatment rimonabant may boost the risk of depression and anxiety.(AFP/File/Paul Ellis)PARIS (AFP) - Two overviews of trials of weight-loss drugs have added to concerns that the obesity treatment rimonabant may boost the risk of depression and anxiety.
The papers, published in Saturday's issue of The Lancet and online Friday by the British Medical Journal (BMJ), follow a decision in June by an advisory panel to the US Food and Drug Administration (FDA) that voted against marketing rimonabant in the United States on safety grounds.
Doctors led by Arne Astrup, a professor at the Faculty of Life Sciences at the University of Copenhagen, analysed four trials in which 4,105 patents were either given a 20mg daily dose of rimonabant or a dummy lookalike pill called a placebo.
Over one year, patients on rimonabant realised a weight loss that was 4.7 kilos (10.3 pounds) higher than counterparts in the placebo group.
But they were also 40 percent likelier to experience "adverse" or "serious adverse" events, according to Astrup's study, which appears in The Lancet.
Patients on rimonabant were two and a half times likelier to stop taking the drug because of depression than those on placebo, and three times likelier to discontinue the treatment because of anxiety.
The findings are significant because individuals with a history of depression -- a phenomenon common among the severely obese -- were specifically excluded from the trial, say the authors.
"We recommend increased alertness by physicians to these potentially severe psychiatric reactions," the Lancet paper says.
Meanwhile, a study published online Friday by the British Medical Journal (BMJ) said that rimonabant and two other anti-obesity drugs, orlistat and sibutramine, were of only limited effect in terms of weight loss over the long term.
Canadian researchers reviewed data from 30 trials in which obese volunteers -- average weight 100 kilos (220 pounds) -- took either anti-obesity drugs or a placebo for a year or more.
The three drugs reduced weight by less than five kilos (11 pounds), equivalent to a loss of less than five percent of total body weight.
The three drugs had various beneficial side effects but all had adverse effects, including, in rimonabant's case, an increase in depression and anxiety, they said.
The authors noted that no trials examined rates of death and disease as a result of taking anti-obesity pills and called for trials to looking into this aspect.
In June, all 14 experts on the FDA's Advisory Committee said rimonabant, which French maker Sanofi-Aventis had hoped would become a blockbuster drug under the brand name of Zimulti, voted against authorising the drug after they heard evidence that it was linked with an increased risk of suicide.
The European Union has approved rimonabant, locally marketed as Acomplia, as a support for diet and exercise for obese patients who have Type 2 diabetes and cardiovascular problems associated with obesity.
However, labelling of the drug has been stepped up to warn against prescribing it to European patients with depression or those taking anti-depressants.
A trial among 1,047 volunteers, published in The Lancet in October 2006, found ribonant improved control over blood glucose and blood fats among people with Type 2 diabetes.
The drug was "generally well tolerated," the study said. Among those volunteers who dropped out of the trial, depression, nausea and dizziness were the most cited reasons among the rimonabant group.Rimonabant blocks endocannabinoid receptors in the brain that cause hunger.Global sales of anti-obesity drugs reached 1.2 billion dollars in 2005, the BMJ said.
Drug Fights Medication-Linked Bone Loss
Drug Fights Medication-Linked Bone Loss
WEDNESDAY, Nov. 14 (HealthDay News) -- An osteoporosis drug has provensuperior to standard therapy at slowing bone loss caused by asthmatreatment, researchers say.
Glucocorticoid medicines such as prednisone are often given to treatasthma, autoimmune disorders, skin allergies and other conditions,researchers note. But the drugs can also cause osteoporosis.
The drug, an anabolic agent called teriparatide, probably will be thepreferable treatment "for patients who have particularly bad disease tostart with or are on glucocorticoids for a long time," said Dr. Kenneth G.Saag, professor of medicine and epidemiology at the University of Alabamaat Birmingham.
The study, which was funded by teriparatide's maker, Eli Lilly &Co., is published in the Nov. 15 issue of the New England Journal ofMedicine.
One million Americans are taking glucocorticoids for one condition oranother, Saag said, and many are at higher risk of fractures, because themedications weaken their bones. Current treatment for medication-linkedosteoporosis centers on use of bisphosphonates, medications designed toprevent bone breakdown.
The 18-month trial included 428 men and women with drug-causedosteoporosis who had been taking glucocorticoids for at least threemonths. Half were assigned to take alendronate, a bisphosphonate, whilethe other half took teriparatide.
After three months, the increase in bone density at the lumbar (lower)spine was double for those taking teriparatide -- an average 7.2 percentrise versus 3.4 percent in the alendronate group. The teriparatide groupalso experienced fewer fractures of the vertebral bones compared withthose on the bisphosphonate.
But teriparatide's much higher cost will limit its use, Saag said. "Useof therapy is driven by insurance as well as by appropriate bone densityand fracture rate," he said. "We would like to be able to single out thosepatients whose minimal bone density puts them at higher risk forfracture," Saag said. "Those patients are the ones we want to target moreaggressively."
That group would include 30 percent to 50 percent of those withdrug-caused osteoporosis, he said. The U.S. Food and Drug Administrationalready has approved use of teriparatide for the treatment of osteoporosisin postmenopausal women at high risk for fracture and to increase bonemass in men at high risk of fracture with primary or hypogonadalosteoporosis.
The anabolic agent is a better treatment, because bisphosphonates donot actually promote bone growth, added Dr. Robert R. Recker, professor ofmedicine at Creighton University and a member of the Osteoporosis ResearchCenter there. Rather, they prevent bone destruction by natural processessuch as apoptosis (natural cell death), he said
"There is a greater need for a bone-forming agent, one that interfereswith the apoptosis of bone cells," Recker said. "The condition is not somuch a low bone mass disease but a disease of bone cells that results intoo much remodeling. Bisphosphonates lower remodeling. [Teriparatide]increases new bone formation."
But longer-term studies are still needed to assess teriparatide'seffects over prolonged periods, Recker said.
"Not one study has gone long enough to see if you get more benefits byusing it for a long time," he said. "It may be good for 24 months. Thatremains to be seen."
More information
WEDNESDAY, Nov. 14 (HealthDay News) -- An osteoporosis drug has provensuperior to standard therapy at slowing bone loss caused by asthmatreatment, researchers say.
Glucocorticoid medicines such as prednisone are often given to treatasthma, autoimmune disorders, skin allergies and other conditions,researchers note. But the drugs can also cause osteoporosis.
The drug, an anabolic agent called teriparatide, probably will be thepreferable treatment "for patients who have particularly bad disease tostart with or are on glucocorticoids for a long time," said Dr. Kenneth G.Saag, professor of medicine and epidemiology at the University of Alabamaat Birmingham.
The study, which was funded by teriparatide's maker, Eli Lilly &Co., is published in the Nov. 15 issue of the New England Journal ofMedicine.
One million Americans are taking glucocorticoids for one condition oranother, Saag said, and many are at higher risk of fractures, because themedications weaken their bones. Current treatment for medication-linkedosteoporosis centers on use of bisphosphonates, medications designed toprevent bone breakdown.
The 18-month trial included 428 men and women with drug-causedosteoporosis who had been taking glucocorticoids for at least threemonths. Half were assigned to take alendronate, a bisphosphonate, whilethe other half took teriparatide.
After three months, the increase in bone density at the lumbar (lower)spine was double for those taking teriparatide -- an average 7.2 percentrise versus 3.4 percent in the alendronate group. The teriparatide groupalso experienced fewer fractures of the vertebral bones compared withthose on the bisphosphonate.
But teriparatide's much higher cost will limit its use, Saag said. "Useof therapy is driven by insurance as well as by appropriate bone densityand fracture rate," he said. "We would like to be able to single out thosepatients whose minimal bone density puts them at higher risk forfracture," Saag said. "Those patients are the ones we want to target moreaggressively."
That group would include 30 percent to 50 percent of those withdrug-caused osteoporosis, he said. The U.S. Food and Drug Administrationalready has approved use of teriparatide for the treatment of osteoporosisin postmenopausal women at high risk for fracture and to increase bonemass in men at high risk of fracture with primary or hypogonadalosteoporosis.
The anabolic agent is a better treatment, because bisphosphonates donot actually promote bone growth, added Dr. Robert R. Recker, professor ofmedicine at Creighton University and a member of the Osteoporosis ResearchCenter there. Rather, they prevent bone destruction by natural processessuch as apoptosis (natural cell death), he said
"There is a greater need for a bone-forming agent, one that interfereswith the apoptosis of bone cells," Recker said. "The condition is not somuch a low bone mass disease but a disease of bone cells that results intoo much remodeling. Bisphosphonates lower remodeling. [Teriparatide]increases new bone formation."
But longer-term studies are still needed to assess teriparatide'seffects over prolonged periods, Recker said.
"Not one study has gone long enough to see if you get more benefits byusing it for a long time," he said. "It may be good for 24 months. Thatremains to be seen."
More information
Diet Drug Rimonabant Tied to Depression, Anxiety
Diet Drug Rimonabant Tied to Depression, Anxiety
THURSDAY, Nov. 15 (HealthDay News) -- People who take the weight-lossdrug rimonabant may face heightened risks for severe depression andanxiety, Danish researchers report.
The finding follows a recommendation by a U.S. Food and DrugAdministration panel in June that the agency not approve the diet drugbecause of continuing concerns about increased risks for suicidal thoughtsamong some users. Previously, the FDA rejected the drug as an aid to helppeople quit smoking.
"Up to this point in time, there has been controversy over the ratesand severity of psychiatric adverse effects with rimonabant," noted Dr.Philip Mitchell, head of the School of Psychiatry at the University of NewSouth Wales in Sydney, Australia, and co-author of an editorial thataccompanies the study.
This is the first review to examine rates of severe psychiatricsymptoms with rimonabant (Acomplia), symptoms severe enough that patientsdiscontinue treatment, Mitchell said.
The report is published in the Nov. 17 edition of TheLancet.
In the meta-analysis, Dr. Arne Astrup, from the department of humannutrition at the University of Copenhagen, collected data on more than4,100 patients enrolled in four clinical trials. Those trials comparedtaking rimonabant (20 milligrams a day) against a placebo.
The researchers found that people taking rimonabant did lose weight --about 15 pounds in a year -- compared to those receiving a placebo.
However, those taking rimonabant were also 40 percent more likely tohave an adverse reaction than people not taking it. In fact, those takingrimonabant were 2.5 times more likely to stop taking the drug because ofdepression and three times more likely to stop the drug because ofanxiety, compared to people on placebo.
"Our findings suggest that 20 milligrams per day of rimonabantincreases the risk of psychiatric events -- i.e., depressed mood disordersand anxiety -- despite depressed mood being an exclusion criterion inthese trials," Astrup's team said. "Taken together with the recent U.S.Food and Drug Administration finding of increased risk of suicide duringtreatment with rimonabant, we recommend increased alertness by physiciansto these potentially severe psychiatric adverse reactions."
Mitchell noted that depression is common in overweight and obesepeople, and is something that doctors need to take into account whenprescribing weight-loss drugs.
"This increased risk of depression and anxiety is a major safety issuein the treatment of obesity, as obese patients already have an increasedrisk of depression even prior to treatment," Mitchell said.
As far as rimonabant is concerned, Mitchell believes doctors shouldconsider alternate weight-loss drugs for people who are depressed. "If oneis using rimonabant, patients should be monitored carefully for theemergence of depressive symptoms and/or suicidal thoughts," he added.
In June, rimonabant's maker, French pharmaceutical giantSanofi-Aventis, said in a statement that despite the FDA's decision, thecompany "is confident in the positive benefit-risk ratio of rimonabant 20milligrams when used in the appropriate population."
Another expert said more data on the safety of rimonabant isneeded.
"Rimonabant is potentially beneficial in some patients, but we reallyneed long-term data demonstrating reductions in major obesity-relatedcomorbidities such as heart attack, stroke and sleep apnea and/ormortality, to be completely certain," said Dr. Raj Padwal, an assistantprofessor of general internal medicine at the University of Alberta inEdmonton, Canada.
The drug needs to be avoided in anyone who has a mood disorder, Padwaladded. "Since many patients with weight issues have depression, this meansthat the drug cannot be used in a large number of people. In the remainingindividuals in whom the drug is used, the patient and physician must becognizant of the risk of a mood disorder and monitor accordingly," hesaid.
In a related study in the Nov. 16 issue of the British MedicalJournal, Padwal's team found that long-term users of weight-loss drugssuch as orlistat (Xenical), sibutramine (Meridia) and rimonabantexperienced only modest weight loss -- less than 11 pounds, which was lessthan 5 percent of their total body weight.
Padwal's team also noted that the U.S. National Institute for ClinicalExcellence recommends stopping the use of weight-loss drugs if 5 percentof total body weight is not lost after three months.
Commenting on Padwal's study, Dr. Gareth Williams, dean of the Facultyof Medicine & Dentistry at the University of Bristol in the U.K.,wrote in an accompanying editorial: "Selling anti-obesity drugs over thecounter will perpetuate the myth that obesity can be fixed simply bypopping a pill and could further undermine the efforts to promote healthyliving, which is the only long-term escape from obesity."
THURSDAY, Nov. 15 (HealthDay News) -- People who take the weight-lossdrug rimonabant may face heightened risks for severe depression andanxiety, Danish researchers report.
The finding follows a recommendation by a U.S. Food and DrugAdministration panel in June that the agency not approve the diet drugbecause of continuing concerns about increased risks for suicidal thoughtsamong some users. Previously, the FDA rejected the drug as an aid to helppeople quit smoking.
"Up to this point in time, there has been controversy over the ratesand severity of psychiatric adverse effects with rimonabant," noted Dr.Philip Mitchell, head of the School of Psychiatry at the University of NewSouth Wales in Sydney, Australia, and co-author of an editorial thataccompanies the study.
This is the first review to examine rates of severe psychiatricsymptoms with rimonabant (Acomplia), symptoms severe enough that patientsdiscontinue treatment, Mitchell said.
The report is published in the Nov. 17 edition of TheLancet.
In the meta-analysis, Dr. Arne Astrup, from the department of humannutrition at the University of Copenhagen, collected data on more than4,100 patients enrolled in four clinical trials. Those trials comparedtaking rimonabant (20 milligrams a day) against a placebo.
The researchers found that people taking rimonabant did lose weight --about 15 pounds in a year -- compared to those receiving a placebo.
However, those taking rimonabant were also 40 percent more likely tohave an adverse reaction than people not taking it. In fact, those takingrimonabant were 2.5 times more likely to stop taking the drug because ofdepression and three times more likely to stop the drug because ofanxiety, compared to people on placebo.
"Our findings suggest that 20 milligrams per day of rimonabantincreases the risk of psychiatric events -- i.e., depressed mood disordersand anxiety -- despite depressed mood being an exclusion criterion inthese trials," Astrup's team said. "Taken together with the recent U.S.Food and Drug Administration finding of increased risk of suicide duringtreatment with rimonabant, we recommend increased alertness by physiciansto these potentially severe psychiatric adverse reactions."
Mitchell noted that depression is common in overweight and obesepeople, and is something that doctors need to take into account whenprescribing weight-loss drugs.
"This increased risk of depression and anxiety is a major safety issuein the treatment of obesity, as obese patients already have an increasedrisk of depression even prior to treatment," Mitchell said.
As far as rimonabant is concerned, Mitchell believes doctors shouldconsider alternate weight-loss drugs for people who are depressed. "If oneis using rimonabant, patients should be monitored carefully for theemergence of depressive symptoms and/or suicidal thoughts," he added.
In June, rimonabant's maker, French pharmaceutical giantSanofi-Aventis, said in a statement that despite the FDA's decision, thecompany "is confident in the positive benefit-risk ratio of rimonabant 20milligrams when used in the appropriate population."
Another expert said more data on the safety of rimonabant isneeded.
"Rimonabant is potentially beneficial in some patients, but we reallyneed long-term data demonstrating reductions in major obesity-relatedcomorbidities such as heart attack, stroke and sleep apnea and/ormortality, to be completely certain," said Dr. Raj Padwal, an assistantprofessor of general internal medicine at the University of Alberta inEdmonton, Canada.
The drug needs to be avoided in anyone who has a mood disorder, Padwaladded. "Since many patients with weight issues have depression, this meansthat the drug cannot be used in a large number of people. In the remainingindividuals in whom the drug is used, the patient and physician must becognizant of the risk of a mood disorder and monitor accordingly," hesaid.
In a related study in the Nov. 16 issue of the British MedicalJournal, Padwal's team found that long-term users of weight-loss drugssuch as orlistat (Xenical), sibutramine (Meridia) and rimonabantexperienced only modest weight loss -- less than 11 pounds, which was lessthan 5 percent of their total body weight.
Padwal's team also noted that the U.S. National Institute for ClinicalExcellence recommends stopping the use of weight-loss drugs if 5 percentof total body weight is not lost after three months.
Commenting on Padwal's study, Dr. Gareth Williams, dean of the Facultyof Medicine & Dentistry at the University of Bristol in the U.K.,wrote in an accompanying editorial: "Selling anti-obesity drugs over thecounter will perpetuate the myth that obesity can be fixed simply bypopping a pill and could further undermine the efforts to promote healthyliving, which is the only long-term escape from obesity."
Sunday, December 30, 2007
New Drug Option for Late-Stage Breast Cancer Patients (American Cancer Society)
New Drug Option for Late-Stage Breast Cancer Patients (American Cancer Society)
There's good news for advanced breast cancer patients whohaven'tresponded to current chemotherapy drugs.
RESOURCES:
Detailed Guide: BreastCancer
UnderstandingChemotherapy: A Guide For Patients And Families
BreastCancer Treatment Decision Tools
After a swift 6-month priority review, the Food and DrugAdministration put its stamp of approval on ixabepilone(IxempraTM), a new chemotherapy drug shown to reduce tumor sizeand slow tumorgrowth in some patients with metastatic or locally advanced breastcancer.
The new drug, developed by Bristol-Myers Squibb, is approved for use incombination with another chemotherapy drug capecitabine, in patientswho haven't had success with an anthracycline (like doxorubicin orepirubicin) and a taxane (like paclitaxel or docetaxel), and as astandalone option for patients who have exhausted all 3 options (ananthracycline, a taxane, and capecitabine).
The FDA review was based on studies of ixabepilone alone andin combination with capecitabine. In a study of 126 breast cancerpatients who received ixabepilone alone, 12% saw a significant decreasein the size of their tumors. In a randomized trial of 752 patients whotook both ixabepilone and capecitabine, tumor growth slowedsignificantly compared to patients who were taking capecitabine alone.
Ixabepilone belongs to a class of drugs known as epothiloneanalogs, which work by binding to and interfering with microtubules,structures that play a key role in cell division. The net effect is aslowing of the growth of cancer cells in the body.
Ixabepilone is given by intravenous infusion over 3 hoursevery 3 weeks. One of the possible side effects of taking ixabepiloneis bone marrow suppression, so it is not recommended for patients whohave low white blood cell or platelet counts. Other possible sideeffects include numbness or tingling in the hands or feet,constipation, nausea, vomiting, and muscle and joint pain.
There's good news for advanced breast cancer patients whohaven'tresponded to current chemotherapy drugs.
RESOURCES:
Detailed Guide: BreastCancer
UnderstandingChemotherapy: A Guide For Patients And Families
BreastCancer Treatment Decision Tools
After a swift 6-month priority review, the Food and DrugAdministration put its stamp of approval on ixabepilone(IxempraTM), a new chemotherapy drug shown to reduce tumor sizeand slow tumorgrowth in some patients with metastatic or locally advanced breastcancer.
The new drug, developed by Bristol-Myers Squibb, is approved for use incombination with another chemotherapy drug capecitabine, in patientswho haven't had success with an anthracycline (like doxorubicin orepirubicin) and a taxane (like paclitaxel or docetaxel), and as astandalone option for patients who have exhausted all 3 options (ananthracycline, a taxane, and capecitabine).
The FDA review was based on studies of ixabepilone alone andin combination with capecitabine. In a study of 126 breast cancerpatients who received ixabepilone alone, 12% saw a significant decreasein the size of their tumors. In a randomized trial of 752 patients whotook both ixabepilone and capecitabine, tumor growth slowedsignificantly compared to patients who were taking capecitabine alone.
Ixabepilone belongs to a class of drugs known as epothiloneanalogs, which work by binding to and interfering with microtubules,structures that play a key role in cell division. The net effect is aslowing of the growth of cancer cells in the body.
Ixabepilone is given by intravenous infusion over 3 hoursevery 3 weeks. One of the possible side effects of taking ixabepiloneis bone marrow suppression, so it is not recommended for patients whohave low white blood cell or platelet counts. Other possible sideeffects include numbness or tingling in the hands or feet,constipation, nausea, vomiting, and muscle and joint pain.
Saturday, December 29, 2007
Pfizer anti-smoking drug under FDA safety review
Pfizer anti-smoking drug under FDA safety review
An ink-stained finger is seen holding on to a cigarette in Amman, Iraq December 14, 2005. The U.S. Food and Drug Administration issued an early warning on Tuesday about Pfizer Inc's anti-smoking drug, Chantix, amid reports of suicidal thoughts and behavior, and at least one death potentially linked to the medication. (Ali Jarekji/Reuters)WASHINGTON (Reuters) - The U.S. Food and DrugAdministration issued an early warning on Tuesday about PfizerInc's anti-smoking drug, Chantix, amid reports of suicidalthoughts and behavior, and at least one death potentiallylinked to the medication.
The FDA is analyzing reports of erratic and aggressivebehavior and suicidal thoughts and behavior in patients takingthe prescription drug, known generically as varenicline.
An early agency assessment "reveals that many of the casesreflect new-onset of depressed mood, suicidal ideation(thoughts) and changes in emotion and behavior within days toweeks" of starting treatment, the FDA said in a posting aboutthe new review.
Under increased scrutiny from lawmakers and consumer groupsfor failing to communicate safety problems with drugs in atimely manner, the FDA has started alerting the public earlierabout a review, even if it has not come to a conclusion.
Many drugmakers claim the agency is taking a tougher stanceon safety following the 2004 withdrawal of Merck & Co Inc'sarthritis drug, Vioxx, and amid recent safety concerns aboutGlaxoSmithKline Plc's diabetes drug, Avandia.
"My first thought is this is another example of the FDAbeing overly safety conscious in light of the withdrawal ofcertain products, such as Vioxx and Avandia," said DamienConover, an analyst at investment research group Morningstar.
But he said it could still be a problem for Chantix.
"When the (attention deficit disorder) drugs got associatedwith increased risk of suicidal thinking, you definitely saw aclass effect of slower growth," he added.
Pfizer, the world's biggest pharmaceutical company,reported revenue of $241 million for Chantix in the thirdquarter of 2007. That is significant, but still not one of itsmajor drugs. It recently launched an ad campaign touting thedrug, which it began selling last year.
CAUSALITY UP IN AIR
The FDA stressed the warning "does not mean that FDA hasconcluded that there is a causal relationship between the drugand the emerging safety issue."
Adverse event reports following a drug's approval arevoluntarily submitted to companies by consumers and doctors andare a very rough indicator of any potential trends, a Pfizerofficial said.
"Postmarketing reports usually do not allow you toestablish a causality because there is very often a significantamount of information missing," said Martina Flammer, a seniormedical director at Pfizer.
She also noted that programs to stop smoking very oftenlead to nicotine withdrawal, which is exacerbated in patientswith psychiatric illness.
The FDA noted, however, that not all patients in the casesnoted had a preexisting psychiatric illness and not all hadstopped smoking.
In its alert, the FDA cited one case of a patient whoseerratic behavior while on the drug lead to death, but addedthat alcohol was also involved.
Doctors are advised to monitor patients taking the drug forchanges in behavior and mood, the FDA said.
Pfizer shares closed up 1 cent at $22.72 on the New YorkStock Exchange.(Reporting by Kim Dixon; additional reporting by ToniClarke and Lewis Krauskopf; editing by Jeffrey Benkoe and AndreGrenon)
An ink-stained finger is seen holding on to a cigarette in Amman, Iraq December 14, 2005. The U.S. Food and Drug Administration issued an early warning on Tuesday about Pfizer Inc's anti-smoking drug, Chantix, amid reports of suicidal thoughts and behavior, and at least one death potentially linked to the medication. (Ali Jarekji/Reuters)WASHINGTON (Reuters) - The U.S. Food and DrugAdministration issued an early warning on Tuesday about PfizerInc's anti-smoking drug, Chantix, amid reports of suicidalthoughts and behavior, and at least one death potentiallylinked to the medication.
The FDA is analyzing reports of erratic and aggressivebehavior and suicidal thoughts and behavior in patients takingthe prescription drug, known generically as varenicline.
An early agency assessment "reveals that many of the casesreflect new-onset of depressed mood, suicidal ideation(thoughts) and changes in emotion and behavior within days toweeks" of starting treatment, the FDA said in a posting aboutthe new review.
Under increased scrutiny from lawmakers and consumer groupsfor failing to communicate safety problems with drugs in atimely manner, the FDA has started alerting the public earlierabout a review, even if it has not come to a conclusion.
Many drugmakers claim the agency is taking a tougher stanceon safety following the 2004 withdrawal of Merck & Co Inc'sarthritis drug, Vioxx, and amid recent safety concerns aboutGlaxoSmithKline Plc's diabetes drug, Avandia.
"My first thought is this is another example of the FDAbeing overly safety conscious in light of the withdrawal ofcertain products, such as Vioxx and Avandia," said DamienConover, an analyst at investment research group Morningstar.
But he said it could still be a problem for Chantix.
"When the (attention deficit disorder) drugs got associatedwith increased risk of suicidal thinking, you definitely saw aclass effect of slower growth," he added.
Pfizer, the world's biggest pharmaceutical company,reported revenue of $241 million for Chantix in the thirdquarter of 2007. That is significant, but still not one of itsmajor drugs. It recently launched an ad campaign touting thedrug, which it began selling last year.
CAUSALITY UP IN AIR
The FDA stressed the warning "does not mean that FDA hasconcluded that there is a causal relationship between the drugand the emerging safety issue."
Adverse event reports following a drug's approval arevoluntarily submitted to companies by consumers and doctors andare a very rough indicator of any potential trends, a Pfizerofficial said.
"Postmarketing reports usually do not allow you toestablish a causality because there is very often a significantamount of information missing," said Martina Flammer, a seniormedical director at Pfizer.
She also noted that programs to stop smoking very oftenlead to nicotine withdrawal, which is exacerbated in patientswith psychiatric illness.
The FDA noted, however, that not all patients in the casesnoted had a preexisting psychiatric illness and not all hadstopped smoking.
In its alert, the FDA cited one case of a patient whoseerratic behavior while on the drug lead to death, but addedthat alcohol was also involved.
Doctors are advised to monitor patients taking the drug forchanges in behavior and mood, the FDA said.
Pfizer shares closed up 1 cent at $22.72 on the New YorkStock Exchange.(Reporting by Kim Dixon; additional reporting by ToniClarke and Lewis Krauskopf; editing by Jeffrey Benkoe and AndreGrenon)
Thailand may get cancer drug free from Novartis: minister
Thailand may get cancer drug free from Novartis: minister
BANGKOK (AFP) - Thailand could get a cancer medicine from Norvatis for free if it slows its drive for generic versions of patented drugs, the country's health minister said Wednesday.
Thailand is at the forefront of an international battle with pharmaceutical companies over so-called compulsory licenses, which temporarily suspend patent protections.
The government has already issued compulsory licenses to get copycat versions of a heart drug and two key AIDS medicines. In September, it announced that it would also seek generic versions of four cancer drugs.
During talks with Novartis over its cancer-fighting Imatinib, Health Minister Mongkol Na Songkhla said the company had offered to provide the drug for free if Thailand halts its drive to expand its generic drug programme.
If a deal were reached, the government could provide unlimited amounts of the drug through its universal health care scheme, he said.
Imatinib currently costs as much as 100,000 baht (2,950 dollars) per patient per month.
"Novartis proposed to us to give free Imatinib without condition and limit in amount and time. We are in the final process of discussion," Mongkol told a seminar on compulsory licensing (CL) in Bangkok.
He said talks with two other drugmakers on cheaper prices for cancer drugs were also making progress.
"If this is successful, there will be no need for the government to implement more CL" on other drugs, he added.
Thailand has so far imposed compulsory licenses for the blockbuster heart drug Plavix and the AIDS medicines Kaletra and Efavirenz.
It has already begun importing cheaper versions from India, a major source of generic drugs.
Mongkol refused to rule out the possibility that the country would seek generic versions of other drugs in extraordinary circumstances.
"I won't say that we will do it again or not. We will do more CL only (on an) exceptional basis," he told reporters.
He also said that the government was considering legal action against Abbott, which withdrew an advanced version of Kaletra from the Thai market after the compulsory license was issued.
Thailand has a law that bars pharmaceutical companies from limiting access to their drugs if the medicine is available in other countries.
"The commerce ministry has been under negotiations with Abbott and considering a chance for legal action against the company," he said.
BANGKOK (AFP) - Thailand could get a cancer medicine from Norvatis for free if it slows its drive for generic versions of patented drugs, the country's health minister said Wednesday.
Thailand is at the forefront of an international battle with pharmaceutical companies over so-called compulsory licenses, which temporarily suspend patent protections.
The government has already issued compulsory licenses to get copycat versions of a heart drug and two key AIDS medicines. In September, it announced that it would also seek generic versions of four cancer drugs.
During talks with Novartis over its cancer-fighting Imatinib, Health Minister Mongkol Na Songkhla said the company had offered to provide the drug for free if Thailand halts its drive to expand its generic drug programme.
If a deal were reached, the government could provide unlimited amounts of the drug through its universal health care scheme, he said.
Imatinib currently costs as much as 100,000 baht (2,950 dollars) per patient per month.
"Novartis proposed to us to give free Imatinib without condition and limit in amount and time. We are in the final process of discussion," Mongkol told a seminar on compulsory licensing (CL) in Bangkok.
He said talks with two other drugmakers on cheaper prices for cancer drugs were also making progress.
"If this is successful, there will be no need for the government to implement more CL" on other drugs, he added.
Thailand has so far imposed compulsory licenses for the blockbuster heart drug Plavix and the AIDS medicines Kaletra and Efavirenz.
It has already begun importing cheaper versions from India, a major source of generic drugs.
Mongkol refused to rule out the possibility that the country would seek generic versions of other drugs in extraordinary circumstances.
"I won't say that we will do it again or not. We will do more CL only (on an) exceptional basis," he told reporters.
He also said that the government was considering legal action against Abbott, which withdrew an advanced version of Kaletra from the Thai market after the compulsory license was issued.
Thailand has a law that bars pharmaceutical companies from limiting access to their drugs if the medicine is available in other countries.
"The commerce ministry has been under negotiations with Abbott and considering a chance for legal action against the company," he said.
Happy in old age: study shows anti-blues drug prolongs life
Happy in old age: study shows anti-blues drug prolongs life
An elderly man checks his e-mail at an Internet cafe for elderly people in Tokyo, July 2007. A commonly-prescribed antidepressant increases the lifespan of worms to the human equivalent of a centenarian, scientists looking for chemicals that prolong longevity reported Wednesday.(AFP/File/Yoshikazu Tsuno)PARIS (AFP) - A commonly-prescribed antidepressant increases the lifespan of worms to the human equivalent of a centenarian, scientists looking for chemicals that prolong longevity reported Wednesday.
What determines lifespan remains poorly understood, but a spate of recent research has begun to unlock mechanisms that could one day adds years and extra pep to the human endgame.
In humans, the antidepressant mianserin prevents the neurotransmitter serotonin from being reabsorbed once it has been released by nerve cells in the brain, thus extending its impact.
Decreased levels of serotonin, a naturally occurring chemical that creates a feeling of well-being, have been linked in many studies to depression.
Linda Buck, a researcher at the Howard Hughes Institute in Seattle, Washington, and two colleagues screened 88,000 chemicals to see which might enhance the lifespan of Caenorhabiditis elegans, a short-lived worm commonly used in experiments on longevity.
In the experiments, a chemical virtually identical to the drug mianserin extended the lives of worms by 30 percent, according to the study.
Three other compounds that also act on serotonin also had a similar effect: mirtazapine, methiothepin and cyproheptadine.
The antidepressant notably blocked uptake of another neurotransmitter, octopamine, which has a role in releasing fat from fat cells.
This links to previous studies showing that lab animals which were kept on a low-calorie diet live longer, said Buck, who won the 2004 Nobel for medicine for research on the human olfactory system.
The findings are not proof that antidepressants can extend life in humans. Rather, they shed light on some of the molecular pathways in the ageing process, say the authors.
"Lifespan can be extended by blocking certain types of neurotransmission implicated in food sensing in the adult animal," Buck said.
An elderly man checks his e-mail at an Internet cafe for elderly people in Tokyo, July 2007. A commonly-prescribed antidepressant increases the lifespan of worms to the human equivalent of a centenarian, scientists looking for chemicals that prolong longevity reported Wednesday.(AFP/File/Yoshikazu Tsuno)PARIS (AFP) - A commonly-prescribed antidepressant increases the lifespan of worms to the human equivalent of a centenarian, scientists looking for chemicals that prolong longevity reported Wednesday.
What determines lifespan remains poorly understood, but a spate of recent research has begun to unlock mechanisms that could one day adds years and extra pep to the human endgame.
In humans, the antidepressant mianserin prevents the neurotransmitter serotonin from being reabsorbed once it has been released by nerve cells in the brain, thus extending its impact.
Decreased levels of serotonin, a naturally occurring chemical that creates a feeling of well-being, have been linked in many studies to depression.
Linda Buck, a researcher at the Howard Hughes Institute in Seattle, Washington, and two colleagues screened 88,000 chemicals to see which might enhance the lifespan of Caenorhabiditis elegans, a short-lived worm commonly used in experiments on longevity.
In the experiments, a chemical virtually identical to the drug mianserin extended the lives of worms by 30 percent, according to the study.
Three other compounds that also act on serotonin also had a similar effect: mirtazapine, methiothepin and cyproheptadine.
The antidepressant notably blocked uptake of another neurotransmitter, octopamine, which has a role in releasing fat from fat cells.
This links to previous studies showing that lab animals which were kept on a low-calorie diet live longer, said Buck, who won the 2004 Nobel for medicine for research on the human olfactory system.
The findings are not proof that antidepressants can extend life in humans. Rather, they shed light on some of the molecular pathways in the ageing process, say the authors.
"Lifespan can be extended by blocking certain types of neurotransmission implicated in food sensing in the adult animal," Buck said.
Thursday, December 27, 2007
Drug Combos Effective Against Rheumatoid Arthritis
Drug Combos Effective Against Rheumatoid Arthritis
MONDAY, Nov. 26 (HealthDay News) -- Combining an older syntheticdrug with a newer, "biologic" medication may work best to ease the jointswelling and tenderness of rheumatoid arthritis, a new study finds.
There are many therapies for rheumatoid arthritis, but the newer drugsare not better than older ones when used alone, the report's authorsfound.
"There are no clinically important differences among the oldersynthetic drugs or among the newer biologic drugs," said lead researcherDr. Katrina E. Donahue, an assistant professor in the department of familymedicine at the University of North Carolina, Chapel Hill. "There arecombination therapies that do work better than using one drug in peoplenot responding to one drug alone," she said.
Combining a synthetic with a biologic appears to work best, Donahuesaid. However, which combinations are most effective still isn't clear. Inaddition, the short-term side effects appear to be the same for both typesof drugs, she added.
In the study, Donahue's team reviewed 23 published studies thatcompared the benefits and harms of different rheumatoid arthritis drugs.These included, synthetic disease-modifying antirheumatic drugs (DMARDs),biologic DMARDs, and corticosteroids.
Synthetic DMARDs include hydroxychloroquine (Plaquenil), leflunomide(Arava), methotrexate (Trexall) and sulfasalazine (Azulfidine). BiologicDMARDs include abatacept (Orencia), adalimumab (Humira), anakinra(Kineret), etanercept (Enbrel), infliximab (Remicade) and rituximab(Rituxan). Corticosteroids include drugs such as prednisone.
Donahue's group found that combining methotrexate with a biologic DMARDworked better than methotrexate or a biologic alone. They also found thatmethotrexate was as effective as the biologics adalimumab and etanerceptin early rheumatoid arthritis.
Adalimumab and etanercept had better short-term results. However,biologics and methotrexate boost the risk of serious infection, includinga reoccurrence of tuberculosis, the researchers found.
Donahue's team also found that prednisone, along withhydroxychloroquine, methotrexate or sulfasalazine worked better inreducing joint swelling and tenderness than using a synthetic DMARDalone.
There was no difference in effectiveness between the synthetic DMARDsmethotrexate, leflunomide and sulfasalazine. And combining methotrexateand sulfasalazine was no more effective than using either one of the drugsalone.
There was also not enough evidence to say whether combining twobiologics was more effective than using one biologic, Donahue said. Forevery 1,000 people taking a biologic for three to 12 months, 17 have aserious infection and combining two biologics can increase that risk, theresearchers noted.
In addition, rates of painful injection site reactions are more commonfor anakinra (67 percent) than for etanercept (22 percent) or adalimumab(18 percent), Donahue's group found.
Donahue recommended that patients talk to their doctors aboutdeveloping a treatment plan that is tailored to their individualcondition. "Rheumatoid arthritis is very patient-specific -- there aremany therapies, and there doesn't appear to be one therapy that is clearlysuperior," she said. "It's a conversation between you and yourrheumatologist about what might be right for you."
One expert said the study will be useful for physicians.
"This is a great summary about what we know about how DMARDs work,"said Dr. Steven Vlad, a fellow in rheumatology at Boston UniversityMedical Center. "That basic finding -- that one synthetic of biologicdoesn't work any better than others -- is a good thing to remind ourselvesof," he said.
Some doctors think that biologics work better, Vlad said. "But that'snot the case. All these drugs seem to work equally as well," he said.
Combination therapy can be effective, Vlad said, but biologics shouldbe the last choice. "Methotrexate is what most doctors are going to gowith first," he said. "You start with methotrexate. If that doesn't work,you add another synthetic drug; if that doesn't work, maybe then you go toa biologic," he said.
More information
For more on rheumatoid arthritis, visit the Arthritis Foundation.
MONDAY, Nov. 26 (HealthDay News) -- Combining an older syntheticdrug with a newer, "biologic" medication may work best to ease the jointswelling and tenderness of rheumatoid arthritis, a new study finds.
There are many therapies for rheumatoid arthritis, but the newer drugsare not better than older ones when used alone, the report's authorsfound.
"There are no clinically important differences among the oldersynthetic drugs or among the newer biologic drugs," said lead researcherDr. Katrina E. Donahue, an assistant professor in the department of familymedicine at the University of North Carolina, Chapel Hill. "There arecombination therapies that do work better than using one drug in peoplenot responding to one drug alone," she said.
Combining a synthetic with a biologic appears to work best, Donahuesaid. However, which combinations are most effective still isn't clear. Inaddition, the short-term side effects appear to be the same for both typesof drugs, she added.
In the study, Donahue's team reviewed 23 published studies thatcompared the benefits and harms of different rheumatoid arthritis drugs.These included, synthetic disease-modifying antirheumatic drugs (DMARDs),biologic DMARDs, and corticosteroids.
Synthetic DMARDs include hydroxychloroquine (Plaquenil), leflunomide(Arava), methotrexate (Trexall) and sulfasalazine (Azulfidine). BiologicDMARDs include abatacept (Orencia), adalimumab (Humira), anakinra(Kineret), etanercept (Enbrel), infliximab (Remicade) and rituximab(Rituxan). Corticosteroids include drugs such as prednisone.
Donahue's group found that combining methotrexate with a biologic DMARDworked better than methotrexate or a biologic alone. They also found thatmethotrexate was as effective as the biologics adalimumab and etanerceptin early rheumatoid arthritis.
Adalimumab and etanercept had better short-term results. However,biologics and methotrexate boost the risk of serious infection, includinga reoccurrence of tuberculosis, the researchers found.
Donahue's team also found that prednisone, along withhydroxychloroquine, methotrexate or sulfasalazine worked better inreducing joint swelling and tenderness than using a synthetic DMARDalone.
There was no difference in effectiveness between the synthetic DMARDsmethotrexate, leflunomide and sulfasalazine. And combining methotrexateand sulfasalazine was no more effective than using either one of the drugsalone.
There was also not enough evidence to say whether combining twobiologics was more effective than using one biologic, Donahue said. Forevery 1,000 people taking a biologic for three to 12 months, 17 have aserious infection and combining two biologics can increase that risk, theresearchers noted.
In addition, rates of painful injection site reactions are more commonfor anakinra (67 percent) than for etanercept (22 percent) or adalimumab(18 percent), Donahue's group found.
Donahue recommended that patients talk to their doctors aboutdeveloping a treatment plan that is tailored to their individualcondition. "Rheumatoid arthritis is very patient-specific -- there aremany therapies, and there doesn't appear to be one therapy that is clearlysuperior," she said. "It's a conversation between you and yourrheumatologist about what might be right for you."
One expert said the study will be useful for physicians.
"This is a great summary about what we know about how DMARDs work,"said Dr. Steven Vlad, a fellow in rheumatology at Boston UniversityMedical Center. "That basic finding -- that one synthetic of biologicdoesn't work any better than others -- is a good thing to remind ourselvesof," he said.
Some doctors think that biologics work better, Vlad said. "But that'snot the case. All these drugs seem to work equally as well," he said.
Combination therapy can be effective, Vlad said, but biologics shouldbe the last choice. "Methotrexate is what most doctors are going to gowith first," he said. "You start with methotrexate. If that doesn't work,you add another synthetic drug; if that doesn't work, maybe then you go toa biologic," he said.
More information
For more on rheumatoid arthritis, visit the Arthritis Foundation.
FDA Mulls Tougher Warning Label on Kids' Flu Drugs
FDA Mulls Tougher Warning Label on Kids' Flu Drugs
TUESDAY, Nov. 27 (HealthDay News) -- A U.S. Food and DrugAdministration panel is meeting Tuesday to debate stronger warninglabeling for the prescription flu drug Tamiflu (oseltamivir), linkedrecently to anecdotal reports of bizarre behaviors and deaths amongchildren.
The FDA's Pediatric Advisory Committee will begin considering labelchanges to Tamiflu and another flu drug, Relenza (zanamivir), when used inchildren.
A safety review released Friday by the FDA's Division of AntiviralProducts does urge stronger label warnings for the medications, includingstricter monitoring of children taking these drugs.
One expert is concerned that the public may overreact, however.
"I am not a fan of replacing fear of a disease with fear of thetreatment for the disease," said Dr. Marc Siegel, a clinical associateprofessor of medicine at New York University School of Medicine in NewYork City. "You don't need to go from one panic to another," he added.
Tamiflu is overused, however, Siegel said. "It's supposed to be used ina very narrow window, and I am not surprised that there have beenpsychiatric side effects related to this drug," he said. "Maybe the newwarning will lead to less overuse," he said.
According to the FDA safety review, there have been 596 reported casesof psychiatric behavior associated with Tamiflu use. Most of these caseshappened among patients 21 or younger. The majority (75 percent) occurredin Japan.
Fifty-nine of the cases were classified as delirium with impulsivebehavior and self-injury. Delirium, delusions, hallucinations or psychosisaccounted for another 225 cases. In total, five children died "as a resultof falls from windows or balconies or running into traffic," the safetyreview found, and three adults committed suicide. So far, there haven'tbeen any such cases reported in the United States, according to theFDA.
The FDA began reviewing Tamiflu in 2005, and, since November 2006, thedrug's label has had a warning focused on self-injury and delirium. Thelabel also advises that patients be monitored during treatment. In Marchof this year, the Japanese Ministry of Health, Labor, and Welfare limitedTamiflu use in patients 10 to 19 years of age.
In their safety review, experts at the FDA advised the committee toamend the label warning to note that there were deaths in Japan related toTamiflu and to strengthen monitoring for patients taking the drug.
However, "A restriction on the use of oseltamivir in the U.S. does notseem warranted at this time based on the post-marketing data and the stillunanswered question about whether these events are due to oseltamivir,influenza/fever, or a combination of the two," the agency safety reviewsaid.
The maker of Tamiflu, Hoffmann-La Roche Inc., of Nutley, N.J., notedthat Tamiflu is used some six times more in Japan than in the UnitedStates. Moreover, whether the bizarre behavior observed is a result of thedrug or the flu itself remains unclear, the company said.
The company sees no need for a label change. "Thus, the information onneuropsychiatric events currently within the Precautions section of theTamiflu [label] continues to be an accurate assessment of all availableupdated and expanded data," it said in a report to the FDA.
Siegel believe a new warning is appropriate. "The idea that there havebeen 596 neuropsychiatric events is a reason for the FDA to put a strongwarning on the label," he said.
Millions of people have taken the drug, so the odds that any onepatient would have these reactions are very low, Siegel said. "People inhigh-risk groups achieve more benefit from the drug [against the flu] thanthey accrue risk for neuropsychiatric events," he said.
Tamiflu is approved both as a preventive and a treatment for flu foradults and children one year and older.
The FDA is also asking the committee to add a similar warning toanother flu drug, Relenza (zanamivir). There have been 115 reported casesof "delirium with impulsive behavior and self-injury in which the patientexpressed 'fear' and attempted to flee or expressed a desire to 'jump,' "the agency said. There were no deaths associated with Relenza, and, aswith Tamiflu, 70 percent of the cases occurred in Japan.
GlaxoSmithKline, the British maker of Relenza, doesn't believe thelabel needs changing. "The review and analysis of all the informationavailable in this safety summary of neuropsychiatric events does notimplicate or indicate a significant causal role of zanamivir. Therefore,no revisions are warranted for the U.S. Prescribing Information and theFDA-approved Patient Labeling for Relenza," the company told the FDA.
Relenza is approved as both a flu preventive and a treatment in adultsand children five years old and older.
In addition, the FDA reviewed side effects associated with two otherflu drugs Symmetrel (amantadine) and Flumadine (rimantadine). They arenot recommending any label changes for these drugs.
More information
For more on flu, visit the U.S. Centers for Disease Control and Prevention.
TUESDAY, Nov. 27 (HealthDay News) -- A U.S. Food and DrugAdministration panel is meeting Tuesday to debate stronger warninglabeling for the prescription flu drug Tamiflu (oseltamivir), linkedrecently to anecdotal reports of bizarre behaviors and deaths amongchildren.
The FDA's Pediatric Advisory Committee will begin considering labelchanges to Tamiflu and another flu drug, Relenza (zanamivir), when used inchildren.
A safety review released Friday by the FDA's Division of AntiviralProducts does urge stronger label warnings for the medications, includingstricter monitoring of children taking these drugs.
One expert is concerned that the public may overreact, however.
"I am not a fan of replacing fear of a disease with fear of thetreatment for the disease," said Dr. Marc Siegel, a clinical associateprofessor of medicine at New York University School of Medicine in NewYork City. "You don't need to go from one panic to another," he added.
Tamiflu is overused, however, Siegel said. "It's supposed to be used ina very narrow window, and I am not surprised that there have beenpsychiatric side effects related to this drug," he said. "Maybe the newwarning will lead to less overuse," he said.
According to the FDA safety review, there have been 596 reported casesof psychiatric behavior associated with Tamiflu use. Most of these caseshappened among patients 21 or younger. The majority (75 percent) occurredin Japan.
Fifty-nine of the cases were classified as delirium with impulsivebehavior and self-injury. Delirium, delusions, hallucinations or psychosisaccounted for another 225 cases. In total, five children died "as a resultof falls from windows or balconies or running into traffic," the safetyreview found, and three adults committed suicide. So far, there haven'tbeen any such cases reported in the United States, according to theFDA.
The FDA began reviewing Tamiflu in 2005, and, since November 2006, thedrug's label has had a warning focused on self-injury and delirium. Thelabel also advises that patients be monitored during treatment. In Marchof this year, the Japanese Ministry of Health, Labor, and Welfare limitedTamiflu use in patients 10 to 19 years of age.
In their safety review, experts at the FDA advised the committee toamend the label warning to note that there were deaths in Japan related toTamiflu and to strengthen monitoring for patients taking the drug.
However, "A restriction on the use of oseltamivir in the U.S. does notseem warranted at this time based on the post-marketing data and the stillunanswered question about whether these events are due to oseltamivir,influenza/fever, or a combination of the two," the agency safety reviewsaid.
The maker of Tamiflu, Hoffmann-La Roche Inc., of Nutley, N.J., notedthat Tamiflu is used some six times more in Japan than in the UnitedStates. Moreover, whether the bizarre behavior observed is a result of thedrug or the flu itself remains unclear, the company said.
The company sees no need for a label change. "Thus, the information onneuropsychiatric events currently within the Precautions section of theTamiflu [label] continues to be an accurate assessment of all availableupdated and expanded data," it said in a report to the FDA.
Siegel believe a new warning is appropriate. "The idea that there havebeen 596 neuropsychiatric events is a reason for the FDA to put a strongwarning on the label," he said.
Millions of people have taken the drug, so the odds that any onepatient would have these reactions are very low, Siegel said. "People inhigh-risk groups achieve more benefit from the drug [against the flu] thanthey accrue risk for neuropsychiatric events," he said.
Tamiflu is approved both as a preventive and a treatment for flu foradults and children one year and older.
The FDA is also asking the committee to add a similar warning toanother flu drug, Relenza (zanamivir). There have been 115 reported casesof "delirium with impulsive behavior and self-injury in which the patientexpressed 'fear' and attempted to flee or expressed a desire to 'jump,' "the agency said. There were no deaths associated with Relenza, and, aswith Tamiflu, 70 percent of the cases occurred in Japan.
GlaxoSmithKline, the British maker of Relenza, doesn't believe thelabel needs changing. "The review and analysis of all the informationavailable in this safety summary of neuropsychiatric events does notimplicate or indicate a significant causal role of zanamivir. Therefore,no revisions are warranted for the U.S. Prescribing Information and theFDA-approved Patient Labeling for Relenza," the company told the FDA.
Relenza is approved as both a flu preventive and a treatment in adultsand children five years old and older.
In addition, the FDA reviewed side effects associated with two otherflu drugs Symmetrel (amantadine) and Flumadine (rimantadine). They arenot recommending any label changes for these drugs.
More information
For more on flu, visit the U.S. Centers for Disease Control and Prevention.
Glaxo asthma drug needs kid risk warning: FDA panel
Glaxo asthma drug needs kid risk warning: FDA panel
GAITHERSBURG, Maryland (Reuters) - U.S. regulatory adviserson Wednesday recommended strengthening safety warnings onGlaxoSmithKline Plc's asthma drug Serevent amid new reports ofdeaths in children taking the drug.
The U.S. Food and Drug Administration expert panel on drugsfor children reviewed nine new adverse event reports in kidstaking the inhaled treatment, including five deaths over aperiod of about a year, among other studies finding increasedhospitalization and asthma-related death in kids.
"The data is very troubling because both the increase inhospitalization and in mortality is so different" from whatdoctors currently believe, said Thomas Newman, anepidemiologist at the University of California, San Francisco,and panel member.
Serevent's use has fallen dramatically since originalreports of asthma deaths came to light a few years back. But itis one ingredient in Glaxo's blockbuster asthma drug Advair,and the new worries could impact that drug, which had $6.8billion in 2006 global sales.
At least two panel members said the data was so convincingthat Serevent should be pulled from the market. The FDA said itwill consider the safety of all drugs in the class, calledlong-acting beta agonists, at a future meeting.
"The members of this committee think this is an urgentpublic health issue," panel chairwoman Dr. Marsha Rappley, aneurology and psychiatry expert at Michigan State University,said.
Novartis also sells a long-acting beta agonist calledForadil.
FDA staffers said no date for the meeting has been set.
Advair contains Serevent plus a steroid. One theorysuggests that the steroid provides a protective effect againstthe negative impact of Serevent, but panel members rejectedthat idea.
"There is not evidence that the steroid mitigates the riskof asthma-related deaths in patients" taking Serevent, Rappleysaid.
In addition to recommending the label more prominentlydisplay the risk of asthma-related deaths, the group said thelabel needs to more prominently show the drug is recommendedonly when other treatments fail.
The FDA typically accepts the recommendations of theseadvisory panels.
Glaxo presented its own set of data rebutting anysuggestion of negative trends when salmeterol, the generic namefor Serevent, is used as directed.
Kathy Rickard, vice president for respiratory clinicaldevelopment at Glaxo, said the company believes data shows noincreased risk of hospitalization and mortality for Advair andshe is not aware of a pending FDA meeting on the issue.
Consumer group Public Citizen lists both drugs on its"worst pills" ranking, arguing their risks outweigh benefits.
Asthma is one of the most common chronic diseases inchildren, marked by restricted breathing and wheezing, andoften made worse by exercise, cigarette smoke and otherfactors.
About 6.5 million children have the condition in the UnitedStates, or about 9 percent of all children, according to theU.S. Centers for Disease Control and Prevention.
GAITHERSBURG, Maryland (Reuters) - U.S. regulatory adviserson Wednesday recommended strengthening safety warnings onGlaxoSmithKline Plc's asthma drug Serevent amid new reports ofdeaths in children taking the drug.
The U.S. Food and Drug Administration expert panel on drugsfor children reviewed nine new adverse event reports in kidstaking the inhaled treatment, including five deaths over aperiod of about a year, among other studies finding increasedhospitalization and asthma-related death in kids.
"The data is very troubling because both the increase inhospitalization and in mortality is so different" from whatdoctors currently believe, said Thomas Newman, anepidemiologist at the University of California, San Francisco,and panel member.
Serevent's use has fallen dramatically since originalreports of asthma deaths came to light a few years back. But itis one ingredient in Glaxo's blockbuster asthma drug Advair,and the new worries could impact that drug, which had $6.8billion in 2006 global sales.
At least two panel members said the data was so convincingthat Serevent should be pulled from the market. The FDA said itwill consider the safety of all drugs in the class, calledlong-acting beta agonists, at a future meeting.
"The members of this committee think this is an urgentpublic health issue," panel chairwoman Dr. Marsha Rappley, aneurology and psychiatry expert at Michigan State University,said.
Novartis also sells a long-acting beta agonist calledForadil.
FDA staffers said no date for the meeting has been set.
Advair contains Serevent plus a steroid. One theorysuggests that the steroid provides a protective effect againstthe negative impact of Serevent, but panel members rejectedthat idea.
"There is not evidence that the steroid mitigates the riskof asthma-related deaths in patients" taking Serevent, Rappleysaid.
In addition to recommending the label more prominentlydisplay the risk of asthma-related deaths, the group said thelabel needs to more prominently show the drug is recommendedonly when other treatments fail.
The FDA typically accepts the recommendations of theseadvisory panels.
Glaxo presented its own set of data rebutting anysuggestion of negative trends when salmeterol, the generic namefor Serevent, is used as directed.
Kathy Rickard, vice president for respiratory clinicaldevelopment at Glaxo, said the company believes data shows noincreased risk of hospitalization and mortality for Advair andshe is not aware of a pending FDA meeting on the issue.
Consumer group Public Citizen lists both drugs on its"worst pills" ranking, arguing their risks outweigh benefits.
Asthma is one of the most common chronic diseases inchildren, marked by restricted breathing and wheezing, andoften made worse by exercise, cigarette smoke and otherfactors.
About 6.5 million children have the condition in the UnitedStates, or about 9 percent of all children, according to theU.S. Centers for Disease Control and Prevention.
FDA Panel Backs Tougher Warning on Asthma Drugs for Kids
FDA Panel Backs Tougher Warning on Asthma Drugs for Kids
TUESDAY, Nov. 27 (HealthDay News) -- A U.S. Food and DrugAdministration advisory panel on Wednesday urged that stronger labelwarnings focused on children be added to the packaging for Serevent andAdvair, two widely used asthma drugs.
Both drugs are long-acting beta agonist medications containingsalmeterol, and are used as asthma prevention in children and adults age 4and up.
But last year -- after a 2005 panel investigation focused mainly on thedrugs' use by adults -- the FDA added a strong "black box" warning on bothmedications that they "may increase the risk of asthma-related death."
The FDA's Pediatric Advisory Committee's new recommendation is thatthis warning be extended specifically to pediatric users of the two drugs,according to Marketwatch, and that it include mention of the factthat the drugs could boost the risk of asthma-linked hospitalizations.
Both drugs are made by GlaxoSmithKline, which said it believed thecurrent black-box warning was sufficient, according to Marketwatch.The FDA says it also plans a new safety review of the two drugs.
Marsha Rappley, chair of the panel, called the recommended labelchange "an urgent public health issue," according to the Wall StreetJournal.
"You need to move forward soon," she told the agency.
The announcement came after the same panel recommended on Tuesday thatthe prescription flu drug Tamiflu (oseltamivir) should have a strongerwarning label to reflect reports of bizarre behaviors and deaths amongchildren who use the medication.
On Wednesday, the drug's manufacturer, Roche, accepted therecommendation, the Associated Press reported.
The panel, in a 9-5 vote, said Roche should change the drug'sprescribing information because it doesn't adequately explain side effectsreported by hundreds of patients in Japan and the United States, accordingto Bloomberg News.
The drug's label mentions reports of delirium and self-injury,primarily among children in Japan, but the advisory panel said thelanguage should state that several patients died as a result of thesebehaviors, AP reported.
A spokeswoman for Roche said Wednesday that all flu patients, not justthose taking Tamiflu, should be warned that the illness posed a risk ofpsychiatric problems. She stressed there was no causal relationshipbetween Tamiflu and the reported cases of delirium and hallucinations,AP reported.
In addition, the FDA panel recommended that labeling for the flu drugRelenza, (zanamivir), should also reflect reports of abnormal behavior,according to Bloomberg.
The FDA is not obliged to follow its expert panels' recommendation, butit usually does. A safety review released Friday by the FDA's Division ofAntiviral Products urged stronger label warnings for both flu drugs,including stricter monitoring of children taking these drugs.
According to the FDA safety review, there have been 596 reported casesof psychiatric behavior associated with Tamiflu use. Most of these caseshappened among patients aged 21 or younger. The majority (75 percent)occurred in Japan.
Fifty-nine of the cases were classified as delirium with impulsivebehavior and self-injury. Delirium, delusions, hallucinations or psychosisaccounted for another 225 cases. In total, five children died "as a resultof falls from windows or balconies or running into traffic," the safetyreview found, and three adults committed suicide. So far, there haven'tbeen any such cases reported in the United States, according to theFDA.
The FDA safety review also reported that in cases involving Relenza,mostly in Japan, there have been 115 reports of "delirium with impulsivebehavior and self-injury in which the patient expressed 'fear' andattempted to flee or expressed a desire to 'jump,'" the agency said. Therewere no deaths associated with Relenza.
During its meeting on Tuesday, the advisory panel said it was unclearwhether the psychiatric problems are a side effect of Tamiflu or the fluitself, AP reported.
At the hearing, representatives of Roche told the panelists that theflu itself, not Tamiflu, caused the bizarre behaviors.
"We feel that the current U.S. prescribing information is an accurateassessment of the current data," Jonathan Solsky, Roche's director of drugsafety risk management, testified, according to Bloomberg.
In a statement released after the meeting, Roche reiterated its faithin the drug. "According to data analyzed from two U.S. claims databases ofmore than 150,000 patients, there is no increased risk forneuropsychiatric events in influenza patients treated with Tamiflucompared to untreated influenza patients," the statement said.
GlaxoSmithKline, the maker of Relenza, also released a statement afterthe meeting. "GSK was pleased to have the opportunity to present safetyinformation on Relenza to the Pediatric Advisory Committee showing noconclusive evidence of a causal association between Relenza andneuropsychiatric events," the statement said.
"We believe the current Relenza U.S. prescribing information accuratelyreflects the safety profile of the drug," the company added.
The FDA first began reviewing Tamiflu in 2005. Since November 2006, thedrug's label has had a warning focused on self-injury and delirium,advising that patients be monitored during treatment. In March, theJapanese Ministry of Health, Labor and Welfare limited Tamiflu use inpatients aged 10 to 19 years old.
Tamiflu is approved both as a preventative and a treatment for flu foradults and children aged 1 year and older.
Relenza is approved as both a flu preventative and a treatment inadults and children aged 5 years old and older.
TUESDAY, Nov. 27 (HealthDay News) -- A U.S. Food and DrugAdministration advisory panel on Wednesday urged that stronger labelwarnings focused on children be added to the packaging for Serevent andAdvair, two widely used asthma drugs.
Both drugs are long-acting beta agonist medications containingsalmeterol, and are used as asthma prevention in children and adults age 4and up.
But last year -- after a 2005 panel investigation focused mainly on thedrugs' use by adults -- the FDA added a strong "black box" warning on bothmedications that they "may increase the risk of asthma-related death."
The FDA's Pediatric Advisory Committee's new recommendation is thatthis warning be extended specifically to pediatric users of the two drugs,according to Marketwatch, and that it include mention of the factthat the drugs could boost the risk of asthma-linked hospitalizations.
Both drugs are made by GlaxoSmithKline, which said it believed thecurrent black-box warning was sufficient, according to Marketwatch.The FDA says it also plans a new safety review of the two drugs.
Marsha Rappley, chair of the panel, called the recommended labelchange "an urgent public health issue," according to the Wall StreetJournal.
"You need to move forward soon," she told the agency.
The announcement came after the same panel recommended on Tuesday thatthe prescription flu drug Tamiflu (oseltamivir) should have a strongerwarning label to reflect reports of bizarre behaviors and deaths amongchildren who use the medication.
On Wednesday, the drug's manufacturer, Roche, accepted therecommendation, the Associated Press reported.
The panel, in a 9-5 vote, said Roche should change the drug'sprescribing information because it doesn't adequately explain side effectsreported by hundreds of patients in Japan and the United States, accordingto Bloomberg News.
The drug's label mentions reports of delirium and self-injury,primarily among children in Japan, but the advisory panel said thelanguage should state that several patients died as a result of thesebehaviors, AP reported.
A spokeswoman for Roche said Wednesday that all flu patients, not justthose taking Tamiflu, should be warned that the illness posed a risk ofpsychiatric problems. She stressed there was no causal relationshipbetween Tamiflu and the reported cases of delirium and hallucinations,AP reported.
In addition, the FDA panel recommended that labeling for the flu drugRelenza, (zanamivir), should also reflect reports of abnormal behavior,according to Bloomberg.
The FDA is not obliged to follow its expert panels' recommendation, butit usually does. A safety review released Friday by the FDA's Division ofAntiviral Products urged stronger label warnings for both flu drugs,including stricter monitoring of children taking these drugs.
According to the FDA safety review, there have been 596 reported casesof psychiatric behavior associated with Tamiflu use. Most of these caseshappened among patients aged 21 or younger. The majority (75 percent)occurred in Japan.
Fifty-nine of the cases were classified as delirium with impulsivebehavior and self-injury. Delirium, delusions, hallucinations or psychosisaccounted for another 225 cases. In total, five children died "as a resultof falls from windows or balconies or running into traffic," the safetyreview found, and three adults committed suicide. So far, there haven'tbeen any such cases reported in the United States, according to theFDA.
The FDA safety review also reported that in cases involving Relenza,mostly in Japan, there have been 115 reports of "delirium with impulsivebehavior and self-injury in which the patient expressed 'fear' andattempted to flee or expressed a desire to 'jump,'" the agency said. Therewere no deaths associated with Relenza.
During its meeting on Tuesday, the advisory panel said it was unclearwhether the psychiatric problems are a side effect of Tamiflu or the fluitself, AP reported.
At the hearing, representatives of Roche told the panelists that theflu itself, not Tamiflu, caused the bizarre behaviors.
"We feel that the current U.S. prescribing information is an accurateassessment of the current data," Jonathan Solsky, Roche's director of drugsafety risk management, testified, according to Bloomberg.
In a statement released after the meeting, Roche reiterated its faithin the drug. "According to data analyzed from two U.S. claims databases ofmore than 150,000 patients, there is no increased risk forneuropsychiatric events in influenza patients treated with Tamiflucompared to untreated influenza patients," the statement said.
GlaxoSmithKline, the maker of Relenza, also released a statement afterthe meeting. "GSK was pleased to have the opportunity to present safetyinformation on Relenza to the Pediatric Advisory Committee showing noconclusive evidence of a causal association between Relenza andneuropsychiatric events," the statement said.
"We believe the current Relenza U.S. prescribing information accuratelyreflects the safety profile of the drug," the company added.
The FDA first began reviewing Tamiflu in 2005. Since November 2006, thedrug's label has had a warning focused on self-injury and delirium,advising that patients be monitored during treatment. In March, theJapanese Ministry of Health, Labor and Welfare limited Tamiflu use inpatients aged 10 to 19 years old.
Tamiflu is approved both as a preventative and a treatment for flu foradults and children aged 1 year and older.
Relenza is approved as both a flu preventative and a treatment inadults and children aged 5 years old and older.
Thai drug users denied access to AIDS treatments: rights group
Thai drug users denied access to AIDS treatments: rights group
This file photo shows a volunteer having his blood tested before the start of a trial on an AIDS vaccine, in Thailand. Thailand is failing to provide treatment to drug users most at risk of AIDS despite its reputation as a pioneer in the global battle against the disease, Human Rights Watch said Thursday.(AFP/File/Pornchai Kittiwongsakul)BANGKOK (AFP) - Thailand is failing to provide treatment to drug users most at risk of AIDS despite its reputation as a pioneer in the global battle against the disease, Human Rights Watch said Thursday.
The Thai government estimates that 40 to 50 percent of injection drug users are living with HIV, a figure that has not changed over the past two decades despite general success in preventing infections, the group said in a report.
"Thailand wants to be seen as a success story in the fight against AIDS, yet it is failing to address the epidemic among the population hit hardest by HIV," said Rebecca Schleifer, an advocate with Human Rights Watch.
"The Thai government has recognised that the HIV infection rate is 'unacceptably high,' and it has the expertise to address this public health emergency," she said.
The report blames the problem on police harassment and discrimination against drug users, saying health care workers deny antiretroviral treatment to people who need it if they are using illicit narcotics.
Many injection drug users were also driven into hiding and afraid of authorities after former premier Thaksin Shinawatra led a "war on drugs" in 2003, when at least 2,500 people died in extrajudicial killings, the group said.
Thailand has generally been lauded for its universal treatment programme, which has included a controversial battle with pharmaceutical companies for cheap or generic versions of cutting-edge treatments.
"An HIV diagnosis is still a death sentence for most drug users in Thailand," said Paisan Suwannawong, director of the Thai AIDS Treatment Action Group.
"Thailand must stop discrimination against drug users seeking health care services, or it will never meet its promise to ensure access to AIDS treatment to all who need it."
This file photo shows a volunteer having his blood tested before the start of a trial on an AIDS vaccine, in Thailand. Thailand is failing to provide treatment to drug users most at risk of AIDS despite its reputation as a pioneer in the global battle against the disease, Human Rights Watch said Thursday.(AFP/File/Pornchai Kittiwongsakul)BANGKOK (AFP) - Thailand is failing to provide treatment to drug users most at risk of AIDS despite its reputation as a pioneer in the global battle against the disease, Human Rights Watch said Thursday.
The Thai government estimates that 40 to 50 percent of injection drug users are living with HIV, a figure that has not changed over the past two decades despite general success in preventing infections, the group said in a report.
"Thailand wants to be seen as a success story in the fight against AIDS, yet it is failing to address the epidemic among the population hit hardest by HIV," said Rebecca Schleifer, an advocate with Human Rights Watch.
"The Thai government has recognised that the HIV infection rate is 'unacceptably high,' and it has the expertise to address this public health emergency," she said.
The report blames the problem on police harassment and discrimination against drug users, saying health care workers deny antiretroviral treatment to people who need it if they are using illicit narcotics.
Many injection drug users were also driven into hiding and afraid of authorities after former premier Thaksin Shinawatra led a "war on drugs" in 2003, when at least 2,500 people died in extrajudicial killings, the group said.
Thailand has generally been lauded for its universal treatment programme, which has included a controversial battle with pharmaceutical companies for cheap or generic versions of cutting-edge treatments.
"An HIV diagnosis is still a death sentence for most drug users in Thailand," said Paisan Suwannawong, director of the Thai AIDS Treatment Action Group.
"Thailand must stop discrimination against drug users seeking health care services, or it will never meet its promise to ensure access to AIDS treatment to all who need it."
Wednesday, December 26, 2007
Overlooked Mutation Can Spur HIV Drug Resistance
Overlooked Mutation Can Spur HIV Drug Resistance
SATURDAY, Dec. 1 (HealthDay News) -- One in 10 HIV-infectedpeople receiving drug treatment harbors a hidden genetic mutation thatrenders certain strains of the virus more resistant to antiretroviralmedications, researchers say.
Their study suggests that the N348I mutation should now be added tostandard HIV gene tests that AIDS specialists use as they decide whichcocktail of drugs a patient should receive.
"The importance of N348I is also underscored by the fact that itappears relatively early after starting drug therapy," noted study seniorauthor Gilda Tachedjian, head of the Molecular Interactions Group at theMacfarlane Burnet Institute for Medical Research and Public Health, inMelbourne, Australia.
The mutation, largely overlooked by researchers, appears to conferresistance to zidovudine (AZT or Retrovir), the first drug ever approvedto fight HIV; and nevirapine (Viramune), one of a group of powerfulantiretroviral medications.
Both medicines fall into a broad category of drugs called reversetranscriptase inhibitors (RTIs), so named because they target a key enzymeon HIV called reverse transcriptase.
Tachedjian's group published its findings late Friday in the Decemberissue of PLoS Medicine on the eve of World AIDS Day.
Gene tests aimed at gauging a particular strain of HIV's resistance tocommon AIDS drugs are routine in clinical practice, noted Mattias Gotte,an associate professor of microbiology and immunology at McGill Universityin Montreal. Gotte is also the author of an accompanying commentary in thejournal.
"You go as an infected person to a clinician, and you get a certainregimen. Most of the time the clinician uses genotyping [gene tests] tosee whether certain preexisting mutations may compromise therapy," heexplained. "The other thing that happens is when you are on a failingregimen. Then, the clinician would genotype the virus and eventually basehis or her decision on the results."
The trick is to match the patient's version of HIV to a group of drugsthat will be least prone to resistance.
In the case of nevirapine and other widely used RTIs, AIDS expertsthought they knew where the key points of resistance lay on the reversetranscriptase molecule, and so they designed their tests accordingly.
"Genotyping assays currently look for drug-resistance mutations in thefirst two-thirds (N-terminal region) of the reverse transcriptase,"Tachedjian explained. "The reason for this is that it is where most of theimportant resistance mutations have occurred."
But there's another region on the enzyme, called the C-terminal, that'salso essential to proper reverse transcriptase function.
"Our logic for the current study was that since the C-terminal regionis involved in how the enzyme 'works,' then it is likely that drugresistance mutations could [also] emerge in this region," Tachedjiansaid.
In their study, her team analyzed samples from more than 1,000 HIVpatients who had received antiretroviral drug therapy. They then comparedtheir results to samples taken from 368 HIV-positive patients who had notyet undergone drug therapy.
The C-Terminal N348I mutation turned up in 12 percent of patients who'dbeen exposed to HIV-suppressing drugs, the researchers report.
In contrast, fewer than 1 percent of the not-treated patients had theresistance-linked mutation -- suggesting that it developed after the virushad been exposed to AIDS drugs.
"The N348I mutation is different from most of the other mutationsdescribed to date because it confers some level of resistance tonevirapine and zidovudine, which are drugs belonging to two differentclasses of reverse transcriptase inhibitors," Tachedjian pointed out."N348I can work alone to confer resistance to nevirapine and zidovudineand can augment resistance when in the presence of other drug mutationsfound in the N-terminal region of the enzyme."
The trouble is, standard genotyping tests are designed to pick upN-terminal mutations but they ignore the C-terminal region, includingN348I.
According to Tachedjian, that means the finding "may have implicationsfor genotypic resistance testing, particularly for patients on zidovudineand nevirapine therapy, and therefore should be considered forincorporation in [standard] genotyping assays."
The advent of new antiretroviral drugs means these gene tests arealready going to have to be altered, she added, "and while we are makingthese changes it could be relatively straightforward to include" theC-terminal region, and N348I, in the tests as well.
Tachedjian believes other overlooked, resistance-conferring mutationsmight also be hiding out in the C-terminal region, and her team iscurrently looking into that possibility.
In the meantime, the N348I discovery could have implications for AIDSdrug development, Gotte pointed out.
"We learn a lot when we study mechanisms of resistance, in terms ofwhat we should avoid in regard to drug development and how we can makedrugs better," he said.
Gotte stressed that HIV-positive patients should not be overlyconcerned that their doctors are missing a key factor as they seek todetermine the best treatment strategy.
While adding N348I to the genotyping mix will improve treatment design,"it's still a minor piece of the puzzle that's missing here," he said. "Iwouldn't be too worried about this because clinicians also look for otherparameters" as they choose effective therapies, he added.
SATURDAY, Dec. 1 (HealthDay News) -- One in 10 HIV-infectedpeople receiving drug treatment harbors a hidden genetic mutation thatrenders certain strains of the virus more resistant to antiretroviralmedications, researchers say.
Their study suggests that the N348I mutation should now be added tostandard HIV gene tests that AIDS specialists use as they decide whichcocktail of drugs a patient should receive.
"The importance of N348I is also underscored by the fact that itappears relatively early after starting drug therapy," noted study seniorauthor Gilda Tachedjian, head of the Molecular Interactions Group at theMacfarlane Burnet Institute for Medical Research and Public Health, inMelbourne, Australia.
The mutation, largely overlooked by researchers, appears to conferresistance to zidovudine (AZT or Retrovir), the first drug ever approvedto fight HIV; and nevirapine (Viramune), one of a group of powerfulantiretroviral medications.
Both medicines fall into a broad category of drugs called reversetranscriptase inhibitors (RTIs), so named because they target a key enzymeon HIV called reverse transcriptase.
Tachedjian's group published its findings late Friday in the Decemberissue of PLoS Medicine on the eve of World AIDS Day.
Gene tests aimed at gauging a particular strain of HIV's resistance tocommon AIDS drugs are routine in clinical practice, noted Mattias Gotte,an associate professor of microbiology and immunology at McGill Universityin Montreal. Gotte is also the author of an accompanying commentary in thejournal.
"You go as an infected person to a clinician, and you get a certainregimen. Most of the time the clinician uses genotyping [gene tests] tosee whether certain preexisting mutations may compromise therapy," heexplained. "The other thing that happens is when you are on a failingregimen. Then, the clinician would genotype the virus and eventually basehis or her decision on the results."
The trick is to match the patient's version of HIV to a group of drugsthat will be least prone to resistance.
In the case of nevirapine and other widely used RTIs, AIDS expertsthought they knew where the key points of resistance lay on the reversetranscriptase molecule, and so they designed their tests accordingly.
"Genotyping assays currently look for drug-resistance mutations in thefirst two-thirds (N-terminal region) of the reverse transcriptase,"Tachedjian explained. "The reason for this is that it is where most of theimportant resistance mutations have occurred."
But there's another region on the enzyme, called the C-terminal, that'salso essential to proper reverse transcriptase function.
"Our logic for the current study was that since the C-terminal regionis involved in how the enzyme 'works,' then it is likely that drugresistance mutations could [also] emerge in this region," Tachedjiansaid.
In their study, her team analyzed samples from more than 1,000 HIVpatients who had received antiretroviral drug therapy. They then comparedtheir results to samples taken from 368 HIV-positive patients who had notyet undergone drug therapy.
The C-Terminal N348I mutation turned up in 12 percent of patients who'dbeen exposed to HIV-suppressing drugs, the researchers report.
In contrast, fewer than 1 percent of the not-treated patients had theresistance-linked mutation -- suggesting that it developed after the virushad been exposed to AIDS drugs.
"The N348I mutation is different from most of the other mutationsdescribed to date because it confers some level of resistance tonevirapine and zidovudine, which are drugs belonging to two differentclasses of reverse transcriptase inhibitors," Tachedjian pointed out."N348I can work alone to confer resistance to nevirapine and zidovudineand can augment resistance when in the presence of other drug mutationsfound in the N-terminal region of the enzyme."
The trouble is, standard genotyping tests are designed to pick upN-terminal mutations but they ignore the C-terminal region, includingN348I.
According to Tachedjian, that means the finding "may have implicationsfor genotypic resistance testing, particularly for patients on zidovudineand nevirapine therapy, and therefore should be considered forincorporation in [standard] genotyping assays."
The advent of new antiretroviral drugs means these gene tests arealready going to have to be altered, she added, "and while we are makingthese changes it could be relatively straightforward to include" theC-terminal region, and N348I, in the tests as well.
Tachedjian believes other overlooked, resistance-conferring mutationsmight also be hiding out in the C-terminal region, and her team iscurrently looking into that possibility.
In the meantime, the N348I discovery could have implications for AIDSdrug development, Gotte pointed out.
"We learn a lot when we study mechanisms of resistance, in terms ofwhat we should avoid in regard to drug development and how we can makedrugs better," he said.
Gotte stressed that HIV-positive patients should not be overlyconcerned that their doctors are missing a key factor as they seek todetermine the best treatment strategy.
While adding N348I to the genotyping mix will improve treatment design,"it's still a minor piece of the puzzle that's missing here," he said. "Iwouldn't be too worried about this because clinicians also look for otherparameters" as they choose effective therapies, he added.
Weigh Roche cancer drug toxicity, say FDA staff
Weigh Roche cancer drug toxicity, say FDA staff
A laboratory researcher in a file photo. Sanofi-Aventis SA sees space in the market for several rivals to Roche Holding AG and Genentech Inc's blockbuster cancer drug Avastin, Sanofi's head of oncology said on Wednesday. (Sebastian Derungs/Reuters)WASHINGTON (Reuters) - The benefits of Roche Holding AG'scancer drug Avastin in breast cancer should be weighed againstsome toxic side effects including the potential for death, U.S.regulatory staffers said in documents released on Monday.
The U.S. Food and Drug Administration staff review comesahead of a Wednesday advisory panel on a bid by Roche and U.S.partner Genentech Inc to extend use of Avastin, alreadyapproved to treat lung and colon cancer, to patients withbreast cancer.
The expert panel will give advice to the FDA on broadeninguse of the drug as a first-line treatment for patients withbreast cancer whose disease has spread.
The drug already reaps blockbuster sales, $2.65 billion inthe first nine months of this year.
In a key trial, the drug failed to extend overall survival,although it did meet its primary goal of extending"progression-free survival," the probability that a patientwill remain alive, without the disease getting worse.
A 5-1/2-month improvement in progression-free survival"must be weighted against the increased toxicity, includingdeaths associated" with the drug, FDA staffers wrote in anexecutive summary, posted on FDA's Web site.
Patients in the study were given either a commonly-usedtreatment called paclitaxel, or paclitaxel combined withAvastin, known generically as bevacizumab.
Among 722 total patients, those in the Avastin group had a20 percent increase in serious toxicity, includinghypertension, blood clots, and heart attacks, among other sideeffects, the FDA staff said.
Death attributed to the drug by the FDA was about 1.7percent of the Avastin group, versus zero in the control group.
The FDA staff disagreed with Genentech's causes of death insome instances.
"Most importantly," staffers wrote, in the Avastin arm"five out of twelve deaths were found to be possibly/definitelyrelated to" treatment.
Roche participation certificates, its most widely tradedform of equity, were 2.5 percent lower at 210.10 Swiss francsby 1439 GMT. Shares of Genentech were down 2.2 percent to$74.57 in morning trade on the New York Stock Exchange.
The briefing documents for the advisory meeting can befound at:http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4332b1-00-index.htm
(Reporting by Kim Dixon; Editing by Tim Dobbyn)
A laboratory researcher in a file photo. Sanofi-Aventis SA sees space in the market for several rivals to Roche Holding AG and Genentech Inc's blockbuster cancer drug Avastin, Sanofi's head of oncology said on Wednesday. (Sebastian Derungs/Reuters)WASHINGTON (Reuters) - The benefits of Roche Holding AG'scancer drug Avastin in breast cancer should be weighed againstsome toxic side effects including the potential for death, U.S.regulatory staffers said in documents released on Monday.
The U.S. Food and Drug Administration staff review comesahead of a Wednesday advisory panel on a bid by Roche and U.S.partner Genentech Inc to extend use of Avastin, alreadyapproved to treat lung and colon cancer, to patients withbreast cancer.
The expert panel will give advice to the FDA on broadeninguse of the drug as a first-line treatment for patients withbreast cancer whose disease has spread.
The drug already reaps blockbuster sales, $2.65 billion inthe first nine months of this year.
In a key trial, the drug failed to extend overall survival,although it did meet its primary goal of extending"progression-free survival," the probability that a patientwill remain alive, without the disease getting worse.
A 5-1/2-month improvement in progression-free survival"must be weighted against the increased toxicity, includingdeaths associated" with the drug, FDA staffers wrote in anexecutive summary, posted on FDA's Web site.
Patients in the study were given either a commonly-usedtreatment called paclitaxel, or paclitaxel combined withAvastin, known generically as bevacizumab.
Among 722 total patients, those in the Avastin group had a20 percent increase in serious toxicity, includinghypertension, blood clots, and heart attacks, among other sideeffects, the FDA staff said.
Death attributed to the drug by the FDA was about 1.7percent of the Avastin group, versus zero in the control group.
The FDA staff disagreed with Genentech's causes of death insome instances.
"Most importantly," staffers wrote, in the Avastin arm"five out of twelve deaths were found to be possibly/definitelyrelated to" treatment.
Roche participation certificates, its most widely tradedform of equity, were 2.5 percent lower at 210.10 Swiss francsby 1439 GMT. Shares of Genentech were down 2.2 percent to$74.57 in morning trade on the New York Stock Exchange.
The briefing documents for the advisory meeting can befound at:http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4332b1-00-index.htm
(Reporting by Kim Dixon; Editing by Tim Dobbyn)
Monday, December 24, 2007
Study questions drug treatments for sinus ills
Study questions drug treatments for sinus ills
CHICAGO (Reuters) - Common drug treatments for sinusinfections -- antibiotics and steroid nasal sprays -- seem tobe little better than doing nothing at all, British researcherssaid on Tuesday.
"Wide-scale overtreatment is likely occurring" becausethere is no proof many of these infections are bacterial innature, Dr. Ian Williamson of the University of Southampton andcolleagues wrote in their report.
Antibiotics are useless against viruses, a common cause ofsinus infections, and their overuse can lead to the developmentof drug-resistant bacteria.
The findings, published in this week's Journal of theAmerican Medical Association, came from a study of 240 adultswith sinus infections between 2001 and 2005.
Some of them were treated with the antibiotic amoxicillinand a nasal spray using the steroid budesonide in each nostril,others got one of those two drugs plus an inert placebo and athird group got two placebos.
After 10 days, 29 percent of those who got the antibioticstill had symptoms compared to 33 percent who did not get thatdrug, and 31 percent who got the spray were still havingproblems compared to 31 percent who did not receive it.
The report said the nasal spray did seem to help patientswho had less severe symptoms to start with.
"Our main conclusions are that among patients with thetypical features of acute bacterial sinusitis, neither anantibiotic nor a topical steroid alone or in combination areeffective in altering the symptom severity, the duration, orthe natural history of the condition," the researchers wrote.
"Topical steroids are likely to be effective in those withsuch features but who have less severe symptoms ..." theyadded.
Even though there is uncertainty about antibiotic use forsinus problems, prescription rates for such drugs for sinustreatment remain as high as 92 percent in the United Kingdomand 85 percent to 98 percent in the United States and are onlyslightly lower in Norway and Holland, the researchers said.
On top of that patients seem to think that antibiotics arethe way to go when it comes to sinus ills, they added.
In a commentary in the same issue, Dr. Morten Lindbaek ofNorway's University of Oslo said some studies indicate thattelling patients to wait a week or so before a prescription canbe filled seems to be one good approach as many patients windup feeling better and not filling the prescriptions.
"Most patients with acute purulent (with pus) sinusitisrecover without antibiotic treatment," he wrote. But in a fewcases patients suffering from fever, malaise and generaldeterioration may still need antibiotics, he added.
In general though, he said, "cautious use of antibiotics inthe general practice setting for patients with sinusitis iswarranted." (Reporting by Michael Conlon; editing by Maggie Foxand Eric Beech)
CHICAGO (Reuters) - Common drug treatments for sinusinfections -- antibiotics and steroid nasal sprays -- seem tobe little better than doing nothing at all, British researcherssaid on Tuesday.
"Wide-scale overtreatment is likely occurring" becausethere is no proof many of these infections are bacterial innature, Dr. Ian Williamson of the University of Southampton andcolleagues wrote in their report.
Antibiotics are useless against viruses, a common cause ofsinus infections, and their overuse can lead to the developmentof drug-resistant bacteria.
The findings, published in this week's Journal of theAmerican Medical Association, came from a study of 240 adultswith sinus infections between 2001 and 2005.
Some of them were treated with the antibiotic amoxicillinand a nasal spray using the steroid budesonide in each nostril,others got one of those two drugs plus an inert placebo and athird group got two placebos.
After 10 days, 29 percent of those who got the antibioticstill had symptoms compared to 33 percent who did not get thatdrug, and 31 percent who got the spray were still havingproblems compared to 31 percent who did not receive it.
The report said the nasal spray did seem to help patientswho had less severe symptoms to start with.
"Our main conclusions are that among patients with thetypical features of acute bacterial sinusitis, neither anantibiotic nor a topical steroid alone or in combination areeffective in altering the symptom severity, the duration, orthe natural history of the condition," the researchers wrote.
"Topical steroids are likely to be effective in those withsuch features but who have less severe symptoms ..." theyadded.
Even though there is uncertainty about antibiotic use forsinus problems, prescription rates for such drugs for sinustreatment remain as high as 92 percent in the United Kingdomand 85 percent to 98 percent in the United States and are onlyslightly lower in Norway and Holland, the researchers said.
On top of that patients seem to think that antibiotics arethe way to go when it comes to sinus ills, they added.
In a commentary in the same issue, Dr. Morten Lindbaek ofNorway's University of Oslo said some studies indicate thattelling patients to wait a week or so before a prescription canbe filled seems to be one good approach as many patients windup feeling better and not filling the prescriptions.
"Most patients with acute purulent (with pus) sinusitisrecover without antibiotic treatment," he wrote. But in a fewcases patients suffering from fever, malaise and generaldeterioration may still need antibiotics, he added.
In general though, he said, "cautious use of antibiotics inthe general practice setting for patients with sinusitis iswarranted." (Reporting by Michael Conlon; editing by Maggie Foxand Eric Beech)
3 Common Drugs Trigger Most ER Visits by Seniors
3 Common Drugs Trigger Most ER Visits by Seniors
TUESDAY, Dec. 4 (HealthDay News) -- Side effects from just three drugsare responsible for a full third of all U.S. emergency room visits bysenior citizens who had adverse reactions to medications, a new studyfound.
In 2004 and 2005, the blood thinner warfarin, the diabetes drug insulinand the heart drug digoxin caused about 58,000 emergency room visits ayear in those 65 and older, the researchers found.
The major problem is that it's hard to determine the correct dose foreach drug, said study lead author Dr. Daniel Budnitz, a medical officerwith the U.S. Centers for Disease Control and Prevention (CDC).
"It's challenging," he said, "and it takes work between the patient andphysician to get the dose just right."
Budnitz and his colleagues undertook the study to determine the dangerposed to senor citizens by a long list of drugs that have been deemed"potentially inappropriate" for use in the elderly.
The researchers looked at several surveys of emergency room visits from2004 and 2005. The study findings are published in the Dec. 4 issue of theAnnals of Internal Medicine.
Forty-one drugs are on the list -- called the BEERS criteria -- ofmedications considered inappropriate for the elderly. But they accountedfor just 3.6 percent of a total of about 177,000 annual emergency roomvisits.
Warfarin (also known as Coumadin), insulin and digoxin (which has anumber of trade names) posed many more problems. (Digoxin is also on thelist of potentially inappropriate drugs for the elderly, but it's onlylisted as a potential problem if taken in certain situations.)
All three medications are well-known, commonly used drugs and all cancreate problems in some cases.
Warfarin, often prescribed to heart patients, prevents blood clots bythinning the blood, but can cause excessive bleeding if the blood becomestoo thin. Insulin treats diabetes but can sometimes cause blood sugarlevels to drop to dangerous levels. And digoxin, a long-used drug, cancause a variety of problems from nausea to erratic heartbeats.
In some cases, there aren't good alternatives to these three drugs,although some doctors consider digoxin to have outlived its usefulness,the study authors noted.
Doctors can monitor the levels of all three drugs with blood tests,Budnitz said. Simple finger-prick blood tests allow testing of blood sugarlevels, and similar tests measuring clotting ability are now available insome clinics for people taking warfarin, he said.
The study results are "a reminder that doctors and patients need towork on doing the best job we can managing these medicines," Budnitz said."The answer isn't to take away medications."
Dr. Knight Steel, head of geriatric medicine at Hackensack UniversityMedical Center in New Jersey, said the study results aren't reallysurprising. Doctors have long known the risks of the three drugs inquestion, he said, adding that the research doesn't provide any newinformation.
TUESDAY, Dec. 4 (HealthDay News) -- Side effects from just three drugsare responsible for a full third of all U.S. emergency room visits bysenior citizens who had adverse reactions to medications, a new studyfound.
In 2004 and 2005, the blood thinner warfarin, the diabetes drug insulinand the heart drug digoxin caused about 58,000 emergency room visits ayear in those 65 and older, the researchers found.
The major problem is that it's hard to determine the correct dose foreach drug, said study lead author Dr. Daniel Budnitz, a medical officerwith the U.S. Centers for Disease Control and Prevention (CDC).
"It's challenging," he said, "and it takes work between the patient andphysician to get the dose just right."
Budnitz and his colleagues undertook the study to determine the dangerposed to senor citizens by a long list of drugs that have been deemed"potentially inappropriate" for use in the elderly.
The researchers looked at several surveys of emergency room visits from2004 and 2005. The study findings are published in the Dec. 4 issue of theAnnals of Internal Medicine.
Forty-one drugs are on the list -- called the BEERS criteria -- ofmedications considered inappropriate for the elderly. But they accountedfor just 3.6 percent of a total of about 177,000 annual emergency roomvisits.
Warfarin (also known as Coumadin), insulin and digoxin (which has anumber of trade names) posed many more problems. (Digoxin is also on thelist of potentially inappropriate drugs for the elderly, but it's onlylisted as a potential problem if taken in certain situations.)
All three medications are well-known, commonly used drugs and all cancreate problems in some cases.
Warfarin, often prescribed to heart patients, prevents blood clots bythinning the blood, but can cause excessive bleeding if the blood becomestoo thin. Insulin treats diabetes but can sometimes cause blood sugarlevels to drop to dangerous levels. And digoxin, a long-used drug, cancause a variety of problems from nausea to erratic heartbeats.
In some cases, there aren't good alternatives to these three drugs,although some doctors consider digoxin to have outlived its usefulness,the study authors noted.
Doctors can monitor the levels of all three drugs with blood tests,Budnitz said. Simple finger-prick blood tests allow testing of blood sugarlevels, and similar tests measuring clotting ability are now available insome clinics for people taking warfarin, he said.
The study results are "a reminder that doctors and patients need towork on doing the best job we can managing these medicines," Budnitz said."The answer isn't to take away medications."
Dr. Knight Steel, head of geriatric medicine at Hackensack UniversityMedical Center in New Jersey, said the study results aren't reallysurprising. Doctors have long known the risks of the three drugs inquestion, he said, adding that the research doesn't provide any newinformation.
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