Avandia
Diabetics taking Avandia advised to consult MDs
Diabetics taking Avandia advised to consult MDs
Updated Wed. May. 23 2007 8:16 AM ET
Canadian Press
TORONTO -- Health Canada says Canadians who are taking the diabetes medication Avandia should not discontinue their medication without first talking to their doctor.
The drug, which was approved in March 2000 in Canada, was the subject of a safety alert in the United States on Monday after a new scientific analysis linked it to a greater risk of heart attack and possibly death.
A spokesperson for Health Canada says patients taking the drug should follow up with their physician to discuss all their risk factors for heart attacks, including the increased risk associated with diabetes.
Jirina Vlk says Health Canada is aware of the study on Avandia in the New England Journal of Medicine and is doing its own analysis of the findings.
As in the United States, Health Canada says there are no immediate plans to change the labelling for the medication.
IMS Health Canada says more than one million prescriptions for the drug were filled in Canada last year, and Avandia was ranked third in the oral diabetes class of drugs.
The retail value of the prescriptions was $156 million in 2006, said Sue Callucci, manager of media and public affairs for IMS, which compiles a national prescription drug database.
Health Canada says the risks and benefits for an individual patient have to be weighed against each other, and compared to those of alternative therapies.
The adverse drug reaction database has received approximately 28 Canadian reports of heart attacks in patients using Avandia since 2000 but "the causal nature of the association of these adverse events with Avandia has not been determined," Health Canada said.
More than six million people worldwide have taken the drug since it came on the market eight years ago. Pooled results of dozens of studies revealed a 43 per cent higher risk of heart attack, according to the review published by the New England Journal of Medicine.
The company downplayed the report of heart risks, saying the analysis by Dr. Steven Nissen and statistician Kathy Wolski at the Cleveland Clinic is not definitive scientific proof. In a conference call Monday, Dr. Lawson McCartney who leads Glaxo's diabetes drug development, said the company is not seeing "anything like" the problems reported in the medical journal.
"We remain very confident in the safety and of course in the efficacy of Avandia as an important diabetic medicine," McCartney said.
U.S. FDA Warned Glaxo in 2001 About Avandia Marketing
U.S. FDA Warned Glaxo in 2001 About Avandia Marketing (Update1)
By Jef Feeley and Michelle Fay Cortez
May 24 (Bloomberg) -- GlaxoSmithKline Plc was warned by U.S. government regulators in 2001 not to downplay heart problems associated with its Avandia diabetes drug that a study published this week linked to an increased risk of heart attacks.
A year earlier, in March 2000, a diabetes expert from the University of North Carolina, Chapel Hill, complained to the Food and Drug Administration about the company's ``rampant abuse of clinical trial data'' related to the drug's cardiovascular safety.
The two documents on the agency's Web site, along with the concerns voiced by its own advisers before the drug reached pharmacy shelves, are providing evidence of early angst about Avandia's impact on the heart. A Cleveland Clinic study released this week found Avandia users were 43 percent more likely to have a heart attack than those given other drugs.
``Any competent plaintiffs lawyer will try to use this to show that Glaxo had a pattern of failing to disclose or downplaying the risks of heart problems tied to Avandia,'' said Alex MacDonald, a Boston-based lawyer who specializes in suing pharmaceutical companies, in an interview yesterday.
Glaxo's shares have fallen 8 percent in London since the Avandia study was announced, shedding more than $13 billion in market value. The company's American depositary receipts, each representing two ordinary shares, fell 61 cents to $53.32 in New York Stock Exchange composite trading yesterday.
Weighing Alternatives
About 7 million people worldwide have taken Avandia and about 1 million Americans currently use it, according to the company. Doctors and patients said they are weighing whether to stick with the pill, while some analysts are predicting a ``broad and rapid decline'' in sales. Avandia, which generated $3 billion last year, was the world's top-selling diabetes drug.
The March 2000 letter from John Buse, director of UNC Chapel Hill's Diabetes Care Center, was mainly devoted to defending the class of diabetes drugs including Avandia. Buse, now president- elect of the American Diabetes Association, also called attention to Avandia's heart risk and its marketing. At the time, Avandia was sold by SmithKline Beecham Plc, which Glaxo bought in 2000.
``They have overstated the safety of the drug with respect to cardiovascular issues,'' Buse wrote, saying the company provided misleading information about its impact on cholesterol and patients with existing heart disease. He also noted ``a worrisome trend in cardiovascular deaths and severe adverse events'' in patients getting Avandia.
Not in the Brochure
The company's glossy brochures, however, didn't reflect the study results, Buse wrote.
``There is something pervasive and systematic that I detect in my travels regarding the marketing'' of Avandia, he wrote. ``Blatant selective manipulation of data has obfuscated relatively straightforward conclusions evident from the FDA data.''
In July 2001, the FDA warned Glaxo in a letter that its marketers should stop denying or minimizing that patients taking the drug with insulin had an increased risk of ``heart failure or other cardiovascular adverse events,'' according to a copy on the FDA's Web site. Regulators criticized Glaxo for continuing to ``engage in false or misleading promotion of Avandia.''
Glaxo spokeswoman Mary Anne Rhyne said in an interview that the company responded to the FDA's letter by cautioning doctors and by making sure marketers disclosed the risks in future presentations.
``We made sure it didn't happen again,'' Rhyne said.
Five Letters
The FDA sent five warning letters to Glaxo in a two-year period starting in 1999 over the company's advertising and marketing of the diabetes drug. It wasn't the first time issues had been raised about Avandia's possible impact on the heart.
A panel of outside FDA advisers voted unanimously on April 22, 1999, that Avandia effectively controlled blood sugar in type 2 diabetics and agreed the drug's safety outweighed its risk. Still, some called for warnings and more studies on heart and liver risks.
``There clearly are some patients that are at risk for substantial worsening of congestive heart failure or fluid retention,'' said panel member Mark Molitch, a professor of medicine at Northwestern University in Chicago. ``This actually should be included in the labeling for the drug, that there may be some people who are at greater risk.''
In February 2001, the company agreed to change Avandia's warning label to show that studies found an increased risk of heart problems for patients taking the drug in combination with insulin. Company officials who knew the risks ``denied their existence'' at a meeting of the American Association of Clinical Endocrinologists, FDA officials noted in the July 2001 letter.
Clarify the Risks
Because of the ``seriousness'' of the company's violations, FDA officials required Glaxo to make the risks clear in letters to doctors and other health-care providers, according to the July 2001 letter.
Executives of London-based Glaxo said this week that numerous, larger studies done on the diabetes drug found no increased risk of heart problems. Avandia is Glaxo's second-best- selling drug after the asthma treatment Advair, sold in some countries as Seretide.
Glaxo's own analysis of its smaller studies showed a 31 percent increased risk of reduced blood flow to the heart, including heart attacks, among patients taking Avandia. The company submitted those findings to the FDA in the summer of 2005 and updated its analysis the following year.
While the data was posted on the company's Web site, Glaxo didn't notify doctors or patients of the possible increase in risks. Subsequent studies, including one that tracked more than 30,000 diabetic patients, found no additional cardiovascular complications, Glaxo said.
Diabetes Patients
Almost 21 million people in the U.S. have diabetes, a disease in which the body doesn't properly make or use the hormone insulin to convert blood sugar to energy, according the American Diabetes Association.
Avandia lowers blood sugar levels, which can cause complications such as kidney and eye damage, by increasing the body's sensitivity to insulin.
Congressional investigators are examining whether the FDA handled the oversight of Avandia properly and have scheduled hearings for June.
FDA officials defend their actions.
``The agency's position on Avandia is that this is a very complicated scientific issue -- the data are evolving and we need to continue to analyze them as quickly as possible,'' FDA spokeswoman Susan Cruzan said in an e-mailed statement yesterday. ``We have been monitoring the drug's safety for some time and are trying very conscientiously and responsibly to inform the public of safety information as we know it and understand it.''
Legal Risks
MacDonald, who has sued other drugmakers, said the warning letters will make it more difficult for Glaxo to use the FDA's approval of the drug to convince jurors it's a safe medicine that was handled properly by the company.
``It's clear from those letters that the FDA had concerns about how the company was advertising and marketing this drug and about the company's response to those concerns,'' said MacDonald, who previously sued Wyeth over injuries caused by its withdrawn diet drugs.
It's too early to tell whether lawsuits over Avandia will match the 27,000 suits filed against Merck & Co. over Vioxx, or the more than 175,000 diet-drug claims Wyeth faced, said MacDonald, a partner in the law firm of MacDonald Rothweiler Eisenberg.
To contact the reporters on this story: Jef Feeley in Wilmington, Delaware at
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