Patients who choose to continue to use the drug must review statements describing the cardiovascular safety concerns associated with Avandia and acknowledge they understand the risks. Their doctors must also attest to and document their patients’ eligibility.

The new rule applies to all drugs containing rosiglitazone, including Avandia , Avandamet (rosiglitazone and metformin) and Avandaryl (rosiglitazone and glimeperide).  GlaxoSmithKline, the maker of Avandia, says it will inform pharmacists and doctors about the new program over the next two months. Patients are advised to discuss their diabetes treatment options with their doctors.

More than 23 million Americans are believed to have type 2 diabetes, and nearly 500,000 Americans filled prescriptions for rosiglitazone in the first 10 months of 2010. At that point, prescriptions dropped considerably as news of the restrictions due to health risk were announced.

SOURCE: Avandia Recall › FDA to remove Avandia from retail pharmacies

A black box warning, or boxed warning, is the strongest warning the FDA can issue and is given to prescription drugs that may cause serious or life threatening health consequences. The boxed warning section describes the risk for congestive heart failure and myocardial infraction, or heart attack, as statistically significant based on clinical trials.

Also added to the warnings and precautions section of the safety information for rosiglitazone are warnings for cardiac failure, adverse cardiovascular events, and fractures. The adverse reactions section was also updated to include a possible increased risk for heart attack when Avandia is used in combination with insulin.

Last fall, the FDA voted to put tight restrictions on Avandia and other drugs in its class based on data from clinical trials that showed use of the drug put patients at risk for cardiovascular events such as heart attacks and strokes. The FDA also ordered makers of the drug to update the product’s safety label to include the warnings. Since the FDA’s ruling, in order for Americans to continue to receive the drug, their doctors must attest to and document their patients’ eligibility. Patients will also have to review statements describing the cardiovascular safety concerns associated with Avandia and acknowledge they understand the risks.

SOURCE: Avandia Recall › FDA approves new warnings on Avandia packaging

GSK was facing about 2,000 lawsuits alleging it covered up Avandia’s heart attack and stroke risks. The company previously agreed to pay about $460 million to resolve allegations it didn’t properly warn doctors and consumers about the medicine’s risk. That news brought more lawsuits against the GSK, and more settlements to the forefront.

The drug was pulled from the European market and severely restricted in the United States last September, after studies linked Avandia to an increased risk for cardiovascular events. This week, the Food and Drug Administration (FDA) approved label changes for Avandia and outlined the standards that patients must meet before they can take the drug.

Those guidelines state that the drug should only be used in patients already being treated with rosiglitazone, in patients whose blood sugar cannot be controlled with other anti-diabetic medications, and who, after consulting with their health care professional, do not wish to use pioglitazone-containing medications, another type of diabetes drug that includes the brands Actos, Actoplus Met, Actoplus Met XR, or Duetact.

Avandia is a single-ingredient product and is also sold as a combination product under the brand name Avandament (with metformin) and the brand name Avandaryl (with glimepride).

Studies suggest as many as 100,000 heart attacks may have been caused by the drug.

SOURCE: Avandia Recall › GSK pays out more money to settle lawsuits against deadly diabetes drug

In order for Americans to continue to receive the drug, their doctors must attest to and document their patients’ eligibility. Patients will also have to review statements describing the cardiovascular safety concerns associated with Avandia and acknowledge they understand the risks. The FDA says it anticipates the tight restrictions will likely have a devastating impact on GlaxoSmithKline’s (GSK) Avandia, the sales of which topped $2 billion last year, down from $3.2 billion in 2006.

Avandia, known by the generic rosiglitazone, is in a class of drugs known as thiazolidinediones, or TZDs. It is intended to be used in conjunction with diet and exercise to improve blood sugar control in patients with Type 2 diabetes mellitus. Rosiglitazone is also available in combination with other diabetes medications, such as metformin under the brand name Avandament or glimepiride under the name Avandaryl.

Despite studies that suggest as many as 100,000 heart attacks may have been caused by Avandia, GSK has long insisted that its billion-dollar drug is safe, going so far as to hold its own study comparing Avandia with a similar medication, Actos. The FDA has ordered GSK to end the study.

The FDA also ordered GSK to convene an independent group of scientists to review key aspects of the company’s clinical trial known as RECORD, which studied the cardiovascular safety of Avandia compared to standard diabetes drugs. During a review of the data, the FDA questioned GSK’s potential bias in the identification of cardiovascular events.

The FDA is continuing to review complaints on the medication. Any side effects with Avandia, or any other medication, should be reported to the FDA Medwatch Adverse Event Reporting Program at www.FDA.gov/Medwatch.

Sources:
New York Times
FDA

SOURCE: Avandia Recall › FDA puts tight restrictions on Avandia due to heart attack, stroke risk

Avandia, also known by the generic name rosiglitazone, faced the same panel in 2007, which voted 22-1 to keep the drug on the market despite a separate vote of 20-3 that there probably was a link to heart problems. Since then, several publications have come out both in support of and against the safety of Avandia. One major topic of this second go-round with the panel includes an analysis of the RECORD study, which the Food and Drug Administration’s Dr. Thomas Marciniak of the division of cardiovascular and renal products wrote, “was inadequately designed and conducted to provide any reassurance about the (cardiovascular) safety of rosiglitazone.”

The 5 ½-year RECORD study involved nearly 5,000 diabetes patients and showed that the drug was not related to an increase in cardiovascular events other than congestive heart failure, which is a documented side effect of drugs used to treat diabetes.

Avandia is a blockbuster medication approved in 1999 to treat Type 2 diabetes, the most common form of the disease. More than a million people in the U.S. have taken the drug. Studies have concluded that Avandia raised the risk of heart attacks in people who used the drug by as much as 43 percent compared to people taking no diabetes medication or other diabetes drugs. Studies have also indicated that Avandia might increase the risk of heart-related deaths.

However, GSK backs the RECORD study, which the FDA argues is “inappropriate and biased.” The panel is expected to vote soon whether to pull the popular diabetes drug off the market.

SOURCE: Avandia Recall › FDA panel to decide fate of diabetes drug Avandia

According to the FDA’s announcement, the “FDA previously communicated to the public about the possible association between rosiglitazone and increased cardiovascular risk in a 2007 safety alert. The agency also sought advice from external experts at the July 30, 2007, joint meeting of the FDA Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees. The RECORD study data represent the only new information from a completed randomized, controlled clinical trial of rosiglitazone received by FDA since the 2007 announcements.”

The RECORD study, which stands for Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes, was designed to evaluate the cardiovascular safety of rosiglitazone. This practice is consistent with the FDA’s December 2008 Guidance for Industry that recommends that manufacturers of new treatments for diabetes carefully design their clinical trials to include an evaluation of cardiovascular safety.

Once the FDA has completed its review of rosiglitazone, the agency will present its findings at a joint public meeting of the Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees in July 2010.

Rosiglitazone, a treatment for Type 2 diabetes, is sold as a single-ingredient product under the brand name Avandia, and is available in combination with other diabetes medications, such as metformin, under the brand name Avandament, or glimepride, under the brand name Avandaryl. The FDA advises that patients who are currently taking any form of rosiglitazone should not stop taking their medication without first talking to their healthcare professional. Any side effects with this or any other medication should be reported to the FDA MedWatch Adverse Event Reporting program at www.fda.gov/medwatch.

SOURCE: Avandia Recall › FDA announces it will review studies linking Avandia to heart attacks

Researchers announced the results of the RECORD trial at the American Diabetes Association meeting in New Orleans. The study monitored 2,220 patients who received Avandia (rosiglitazone) as a supplement to metformin, normally the first-line drug in diabetes 2 treatment, or sulphonylurea. 2,227 other patients received a combination of metformin and sulphonylurea without Avandia.

GlaxoSmithKline said the findings confirmed that “cardiovascular hospitalization and cardiovascular death was not statistically different between the two groups after an average of 5.5 years of therapy.”

Philip Home, a professor at Newcastle University in Newcastle Upon Tyne in the UK and chairman of the RECORD trial, said the data “leads us to conclude that rosiglitaone carries no increased risk of overall cardiovascular death or hospitalization compared to the most commonly used diabetes medicines…which have been used for decades.”

However, an editorial by Toronto doctors Ravi Retnakaran and Bernard Zimman in the medical journal The Lancet, in which the RECORD results were published, raised doubts about the study’s accuracy. The doctors wrote that “definitive conclusions about the relation between rosiglitazone and cardiovascular disease remain elusive, owing to study limitations.”

The overall rate of cardiovascular problems in the RECORD patients was unusually low, and ten percent more of the Avandia patients were taking statins – cholesterol fighting drugs that effectively reduce the risk of heart attack.

Moreover, 45 percent of the RECORD participants dropped out of the study at some point, yet Glaxo maintains that the high dropout rate did not influence the results. Doctors Retnakaran and Zimman believe that dropout rate alone compromises the trial’s conclusions.

Steven E. Nissen, M.D. of the Cleveland Clinic said that “it is impossible to assess the safety of a drug when patients are not actually taking it.”

SOURCE: Avandia Recall › Doctors and critics doubt the accuracy of Avandia study