Avandia is a drug manufactured by GlaxoSmithKline
and prescribed by doctors for the treatment of Type 2 Diabetes
and is also known by its generic name, rosiglitazone or rosiglitazone maleate.
Recently, there have been several serious warnings about drugs containing rosiglitzone, including Avandia, issued by the U.S. Food and Drug Administration (FDA), the government agency that oversees pharmaceutical safety.
The FDA has issued the following warnings to patients:
- Patients should be informed about the possible increased risk of myocardial ischemia (which includes events such as angina (heart pain) or myocardial infarction (heart atttack).
- Patients should be asked if they are taking insulin or nitrates and informed that taking rosiglitazone and insulin or rosiglitazone with nitrates may increase the risk of myocardial ischemia.
- Patients should be asked to watch for and report immediately to a healthcare professional any signs and symptoms of myocardial ischemia, including chest pain or pressure, or pain that radiates to the jaw or down the arm, and shortness of breath. Such symptoms may require urgent medical treatment.
- Patients should be informed that Avandia, Avandamet, and Avandaryl, alone or in combination with other antidiabetic agents, can cause fluid retention, which may exacerbate or lead to heart failure.
- Patients should be asked to watch for and report to their healthcare professional any signs and symptoms of heart failure, including edema from fluid retention, shortness of breath or trouble breathing, unusually fast increase in weight, and unusual tiredness.
These warnings appear, in part, in the updated “boxed” label (the FDA’s “strongest form of a warning”) or “Black Box Warning
” that appears on the prescription instructions for Avandia
The Food and Drug Administration (FDA) ordered GSK to halt enrolling new patients in a safety study of Avandia
, a week after a panel of experts ruled the drug increases heart risks.
The “partial clinical hold” will allow researchers to study new evidence of Avandia’s risks. This month, a panel of experts voted that the drug appears to raise heart risks, but ultimately voted to leave the drug on the market because the evidence is inconclusive.
The FDA is currently reviewing the panel’s opinions and deciding what action to take. It is expected to make a decision on whether to keep the drug on the market in coming months.
The first trial set in the U.S. on Avandia’s link to heart attacks
, as well as other serious side effects, settled just hours before the trial was set to begin on June 1, in Philadelphia.
GlaxoSmithKline faces more about 13,000 claims for injuries from its diabetes drug, Avandia, estimates analysts. Several of the claims were consolidated in Philadelphia and about half have now been settled.
The next case scheduled for trial is in October 2010.November 2007
On November 19, 2007, the U.S. Food and Drug Administration issued an Updated Alert
highlighting changes to the prescribing information and a new BOXED WARNING that changes the Warnings, Precautions, and Indications sections of the label to add a new warning about the risk of myocardial ischemia
angina, acute chest pain, and heart failure).
avandia fda black box warning label congestive heart failure mycardial ischemia november 21 2007
On August 14, 2007, the U.S. Food and Drug Administration issued another FDA Alert
about rosiglitazone maleatcone (marketed as Avandia, Avandamet, and Avandaryl) announcing a new, stronger “boxed” warning to patients and health care providers.
avandia fda black box warning congestive heart failure august 14 2007
The alert included,
“…a stronger warning on the risk of heart failure, a condition that occurs when the heart does not adequately pump blood… The upgraded warning emphasizes that the drugs may cause or worsen heart failure in certain patients.”
The alert states that the new, stronger warning came as a result of an FDA review of postmarketing adverse event reports It includes this statement from Steven Galson, MD, MPH, director of the FDA’s Center for Drug Evaluation and Research,
“This new boxed warning addresses FDA's concerns that despite the warnings and information already listed in the drug labels, these drugs are still being prescribed to patients without careful monitoring for signs of heart failure."
The alert concludes with the statement that, “FDA's review of Avandia and possible increased risk of heart attacks is ongoing”
and refers to the findings of the July 30, 2007 recommendations (see below).
On July 30, 2007, the FDA convened a joint meeting
of the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) met to,
"...consider the evidence for increased cardiac ischemic risk for rosiglitazone and to advise CDER on whether the drug product should remain on the market. The Committee recommended that rosiglitazone remain on the market and that information about ischemic cardiovascular risks be added to the label." (emphasis added)
On June 18, 2007, the FDA issued a Consumer Update
with new safety information for patients taking rosiglitazone. The update began with this notice,
“Concerns are being raised about a possible increased chance of heart attack and heart-related deaths in patients taking rosiglitazone, an ingredient in three drugs used to treat type 2 diabetes: Avandia, Avandaryl, and Avandamet.”
Later in the update, the FDA states,
“There is agreement by several organizations that the overall level of risk appears to be small, but that the risk deserves serious attention and follow-up. They are:
- American Association of Clinical Endocrinologists
- American College of Cardiology
- American Diabetes Association
- American Heart Association
- Endocrine Society
“FDA agrees with these organizations and is conducting a thorough investigation.”
The FDA suggested the following steps for patients,
- Do not stop taking Avandia, Avandaryl or Avandamet without first talking to your doctor about this new information.
- Discuss the best individualized treatment plan for your diabetes and other medical conditions.
- Remember that the best treatment plan is a team approach between you and your doctor.
On May 21, 2007, the U.S. Food and Drug Administration issued an FDA Alert
to healthcare professionals about Avandia, reporting that
“…controlled clinical trials have shown that there is a potentially significant increase in the risk of heart attack and heart-related deaths in patients taking Avandia. However, other published and unpublished data from long-term clinical trials…provide contradictory evidence about the risks in patients treated with Avandia.”
“The pooled analysis suggested that patients receiving short-term (most studies were 6-months duration) treatment with Avandia may have a 30-40 percent greater risk of heart attack and other heart-related adverse events than patients treated with placebo or other anti-diabetic therapy. These data, if confirmed, would be of significant concern since patients with diabetes are already at an increased risk of heart disease.”
The FDA ALERT included this warning,
“Patients who are taking Avandia, especially those who are known to have underlying heart disease or who are at high risk of heart attack should talk to their doctor about this new information as they evaluate the available treatment options for their type 2 diabetes.”
On May 21, 2007, the New England Journal of Medicine released an Research Article entitled, “Effect of Rosiglitazone on the Risk of Mycardial Infarction and Death from Cardiovascular Causes” in which authors Steven E. Nissen, MD
and Kathy Wolski, MPH concluded,"Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance
Nissen is a cardiologist with the Cleveland Clinic’s Heart and Vascular Institute
whose research of clinical drug test data has led the Wall Street Journal
VIDEO: Steven E. Nissen, MD is interviewed about his article on rosigliatazone (Avandia)
“Merck’s painkiller Vioxx was withdrawn from the market and development of Merck’s and Bristol-Myers Squibb’s diabetes drug Pargluva was shelved in the wake of his analyses.”
In the month following the release of Nissen's analysis, reports of Avandia-related side effects tripled across the country, according to an article in The Washinton Post. Based on documents received by the Associated Press, reports of myocardial infarction related to Avandia went from 11 to 126 in slightly over a month.
The paper reported that several experts believe,
“The sudden spike is a sign that doctors probably were unaware of the drug’s possible role in their patient’s heart problems and therefore may not have reported many such cases in the past…”
But, a spokesperson from the manufacturer GlaxoSmithKline saw the increased reporting as normal because of the increased media attention and the greater number of adverse incidents inconclusive,
"This is a very well-known phenomenon… It's good that there's awareness of the reporting system, but drawing conclusions on such data is inappropriate."
On January 22, 2002, the Canadian Medical Association Journal (CMAJ) issued a Health and Drug Alert
article warning the medical community of
“...an increasing number of reports of congestive heart failure (CHF), pulmonary edema and pleural effusion suspected to be associated with the diabetic agents rosiglitazone and pioglitazone”.
In February 2001, the FDA required Glaxo to change the Avandia side effects label to reflect the increased risk of cardiac failure
in patients combining Avandia with insulin. Studies indicate that concurrent use of Avandia and insulin can result in fluid-overload disease, which in turn may lead to heart failure and death
Avandia, also known as rosiglitazone, is a drug
used to treat type II diabetes
. Avandia is a thiazolidinedione class drug manufactured by Glaxo Smith Kline Pharmaceuticals. The drug assists the body in utilizing insulin. The FDA approved Avandia in 1999.
Avandia is similar to Rezulin
, another type II thiazolidinedione class diabetes drug
that was withdrawn from the market because of its tendency to cause liver failure
. There is some concern that side effects of Avandia for diabetes may include an increased risk of developing liver problems.
Over 2 Million people are prescibed Avandia each year. The diabetes drug
delivers an estimated $3.2 Billion in sales
to its maker, GlaxoSmithKline, which strongly disputes the Avandia research
and its methods. ConsumersUnion.org
, an independent nonprofit organization whose mission is to work for a fair, just, and safe marketplace for all consumers, released an urgent statement calling for Congress to address Drug Safety Reform
and greater oversight of pharmaceutical companies.
NEXT STEPSLEARN MORE
about Avandia at the FDA websiteREPORT ADVERSE REACTIONS
or serious events associated with Avandia or any other prescription drug directly with FDA’s MedWatch program.FORMATTER ERROR (Malformed Image Tag)