February 26, 2008

Audience: Endocrinologists, pharmacists, patients
[Posted 02/26/2008] FDA and GlaxoSmithKline notified pharmacists and physicians of a new Medication Guide for Avandia (rosiglitazone maleate). The FDA regulation 21CFR 208 requires a Medication Guide to be provided with each prescription that is dispensed for products that FDA determines pose a serious and significant public health concern. A list of currently approved Medication Guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm. The Medication Guide and current Prescribing Information for Avandia are provided below.

Product Description

Most important information about Avandia

Pharmacokinetics

Possible Side Effects

More information about AVANDIA (Rosiglitazone):

AVANDIA (Rosiglitazone): What You Should Know

Can Avandia or other drugs prevent diabetes?

Actos beats Avandia in sugar, fat control: study

Avandia approved for combination with insulin in type 2 diabetes treatment

Avandia Reduces Risk of Progresson from Pre-Diabetes to Type 2 Diabetes by 62 percent

EMEA Statement on Recent Publication on Cardiac Safety of Rosiglitazone (Avandia, Avandamet, Avaglim)

GSK Revises US Labeling for Avandia

Data Affirms Avandia (Rosiglitazone maleate) Cardiovascular Safety Profile

Reaction to Avandia Warnings Stronger Among Internists Than Endocrinologists, According to Study by GfK Market Measures

Texas Family Sues GlaxoSmithKline (GSK) Over Man’s Heart Attack Death Following Avandia Use

Older Diabetics Using Avandia Face Increased Death Risk

To buy AVANDIA click HERE: My Family Drugstore

Researchers who analysed data on 78,000 patients who took Avandia or Actos to treat type II diabetes found that it increased the risk of heart failure by up to 100 percent, said the study released on Thursday.

The researchers estimate that for every 50 patients taking the medications over a period of 26 months, one person will develop heart failure.

The manufacturers cautioned from the beginning that the drugs were not suitable for patients at risk for – or with a history of – heart failure, and that patients who combined the drugs with insulin treatments were at increased risk for this complication.

But this analysis found that this adverse effect occurred in patients with no risk for heart failure, even in the absence of insulin. The study also showed that it occurred in young people and at high and low doses.

On average, patients who developed this complication did so 24 weeks after starting on the drug, the investigators report in the journal Diabetes Care.

“Our analysis quantifies the risk for the first time and it shows that nobody is immune,” said Sonal Singh, lead author of the study and an assistant professor in internal medicine at Wake Forest University Baptist Medical Center in Winston Salem, North Carolina.

Singh said the findings raise the question of whether doctors should revert to using older drugs such as Glucophage and or insulin injections.

The researchers did not evaluate whether the adverse effects were fatal, nor did they study what went wrong. They suggest that the drugs cause some people to retain fluid which can trigger heart failure, symptoms of which include shortness of breath and an inability to exercise.

GlaxoSmithKline, which has been marketing Avandia in the United States since 1999 and in Europe since 2000, downplayed the findings. Actos is made by Takeda Pharmaceutical.

“The risk of heart failure in diabetes patients and with use of these medicines is well recognized and is clearly identified in prescribing information to doctors,” the company said in a statement.

“GSK is confident in the overall safety profile of rosiglitazone when used appropriately.”

Rosiglitazone is the trade name for Avandia.

GSH’s blockbuster drug has also been linked with other problems. In May, a study in a US medical journal said people taking the drug had a 43 percent higher risk of heart attack.

The US Food and Drug Administration will consult with medical experts on Monday to see whether the data merits adding so-called “black box warnings” to the drug packaging that would alert consumers to the potential risk.

Product Description

Most important information about Avandia

Pharmacokinetics

Possible Side Effects

More information about AVANDIA (Rosiglitazone):

AVANDIA (Rosiglitazone): What You Should Know

Can Avandia or other drugs prevent diabetes?

Actos beats Avandia in sugar, fat control: study

Avandia approved for combination with insulin in type 2 diabetes treatment

Avandia Reduces Risk of Progresson from Pre-Diabetes to Type 2 Diabetes by 62 percent

EMEA Statement on Recent Publication on Cardiac Safety of Rosiglitazone (Avandia, Avandamet, Avaglim)

GSK Revises US Labeling for Avandia

Data Affirms Avandia (Rosiglitazone maleate) Cardiovascular Safety Profile

Reaction to Avandia Warnings Stronger Among Internists Than Endocrinologists, According to Study by GfK Market Measures

Texas Family Sues GlaxoSmithKline (GSK) Over Man’s Heart Attack Death Following Avandia Use

Older Diabetics Using Avandia Face Increased Death Risk

FDA MedWatch Alerts: Avandia (rosiglitazone maleate)

To buy AVANDIA click HERE: My Family Drugstore

Rosiglitazone (Avandia) and pioglitazone (ACTOS) are in a group of drugs called thiazolidinediones. These drugs help insulin work better in the muscle and fat and also reduce glucose production in the liver. The first drug in this group, troglitazone (Rezulin), was removed from the market because it caused serious liver problems in a small number of people. So far rosiglitazone and pioglitazone have not shown the same problems, but users are still monitored closely for liver problems as a precaution. Both drugs appear to increase the risk for heart failure in some individuals, and there is debate about whether rosiglitazone may contribute to an increased risk for heart attacks. Both drugs are effective at reducing A1C and generally have few side effects.

Product Description

Most important information about Actos

Pharmacokinetics

Side Effects

More information about ACTOS (Pioglitazone):

FDA Alert

Actos Benefits Recent Heart-Attack Patients with Diabetes

Actos found to improve glucose control and lipid profiles

Takeda Revises Actos (pioglitazone HCl) Prescribing Label

New Analyses Show Actos Reduced Risk of Secondary Stroke by Almost 50 Percent

ACTOS (Pioglitazone) Combination Therapy

Submission of an Application for an additional Indication of Actos in Japan; Concomitant Therapy with Biguanides for Type 2 Diabetes

Termination of Development of Fixed Dose Combination Product of Actos + TAK-536

Takeda Wins Patent Infringement Litigation on Appeal Against ANDA Filers for Generic Actos

Diabetes Drugs Increase Risk of Heart Failure, Research Shows

To get more information about Actos: ACTOS MEDICATION.

To buy ACTOS click HERE: My Family Drugstore

Rosiglitazone (Avandia) and pioglitazone (ACTOS) are in a group of drugs called thiazolidinediones. These drugs help insulin work better in the muscle and fat and also reduce glucose production in the liver. The first drug in this group, troglitazone (Rezulin), was removed from the market because it caused serious liver problems in a small number of people. So far rosiglitazone and pioglitazone have not shown the same problems, but users are still monitored closely for liver problems as a precaution. Both drugs appear to increase the risk for heart failure in some individuals, and there is debate about whether rosiglitazone may contribute to an increased risk for heart attacks. Both drugs are effective at reducing A1C and generally have few side effects.

Product Description

Most important information about Avandamet

Pharmacokinetics

Possible Side Effects

More information about AVANDAMET (Rosiglitazone/Metformin):

FDA MedWatch Alerts

Combination with Insulin

FDA Approves Avandamet as Initial Therapy for Type 2 Diabetes

FDA Alert

Too Many Meds: Try Combinations

New Avandamet dosage strengths approved for treatment of type 2 diabetes

EMEA Statement on Recent Publication on Cardiac Safety of Rosiglitazone (Avandia, Avandamet, Avaglim)

To get more information about Avandamet: AVANDAMET MEDICATION.
To buy AVANDAMET (Rosiglitazone/Metformin) click HERE: My Family Drugstore

GlaxoSmithKline, the maker of Avandia (rosiglitazone), a drug used to treat type 2 diabetes, has agreed to add the new warning to the existing black box warning on the drug’s label, according to U.S. Food and Drug Administration officials.

“We are announcing an update to the existing box warning on Avandia,” Dr. Janet Woodcock, acting director of the FDA’s Center for Drug Evaluation and Research, said during a midday teleconference. “A black box is the strongest form of warning, and we are adding another warning to that black box.”

Despite the revised warning label, the FDA said it isn’t seeking to have the drug withdrawn from the market, because the evidence for the increased heart-attack risk is not conclusive.

“We are keeping Avandia on the market, because we have concluded there isn’t enough evidence to indicate that the risk of heart attack is higher for Avandia than other type 2 diabetes treatments,” Woodcock said.

Woodcock said the FDA has asked GlaxoSmithKline to conduct a long-term study comparing Avandia with other type 2 diabetes drugs. The trial will most likely start in a year, and full results won’t be available until 2014.

Dr. Steven Nissen, chairman of the Cleveland Clinic’s department of cardiovascular medicine, first raised concerns about Avandia and heart-attack risk in a study published earlier this year. He said he welcomed “the addition of a black box warning for the risk of heart attack from Avandia,” but would have preferred a warning “written with greater clarity,” like the one used by Health Canada, the FDA’s counterpart in Canada.

The Canadian labels says Avandia is not to be used as the sole medication for type 2 diabetes except for patients who can not take another drug — metformin — that also lowers blood sugar. The label also states that Avandia is not to be used by any patient with heart failure.

“This is a much clearer statement than the FDA statement,” Nissen said.

Nissen said he was also bothered by the proposed trial that ends in 2014. “It really doesn’t solve the problem of what to do in the meantime,” he said. “I hope the appearance of a black box warning will be enough to keep people from being harmed.”

The new FDA-mandated labeling change follows recommendations made by the FDA’s Endocrine and Metabolic Advisory Committee and Drug Safety and Risk Management Advisory Committee. In July, the committees recommended keeping Avandia on the market, pending a review of additional data. The committees also said the drug’s label should carry a warning of the potential for increased risk of heart attacks.

Controversy over Avandia started in May, when a study by Nissen and colleague Kathy Wolski, published in the New England Journal of Medicine, found a 43 percent increased risk of heart attack among patients taking the drug. Nissen said he uncovered the risk after poring over data from 42 studies of Avandia.

Both the FDA and GlaxoSmithKline continue to say that the evidence for the risk of heart attack with Avandia is inconclusive.

“Avandia remains a safe and effective medicine for most patients with type 2 diabetes when used appropriately,” Dr. Ronald Krall, GlaxoSmithKline’s chief medical officer, said in a prepared statement. “Given the severity of this disease and the importance of Avandia in helping patients manage their diabetes, we will continue to work with the FDA to conduct more studies about the safety and benefits of our medicine.”

The new warning states: “A meta-analysis of 42 clinical studies (mean duration 6 months; 14,237 total patients), most of which compared Avandia to placebo, showed Avandia to be associated with an increased risk of myocardial ischemic events such as angina or myocardial infarction. Three other studies (mean duration 41 months; 14,067 patients), comparing Avandia to some other approved oral anti-diabetic agents or placebo, have not confirmed or excluded this risk. In their entirety, the available data on the risk of myocardial ischemia are inconclusive.”

The FDA is advising people with type 2 diabetes who have heart disease or are at risk of a heart attack to discuss their use of Avandia with their doctor to evaluate treatment options. The agency is also advising doctors to monitor patients who have cardiac risk and are taking the drug.

In August, Avandia’s warning label was changed, to state that the drug and others in its class may worsen heart failure — a condition in which the heart does not adequately pump blood — in some patients. The association between Avandia and increased risk for heart failure has been known since 1999, when the drug was first approved.

Woodcock noted that Avandia and the other oral anti-diabetes drugs, called thiazolidinediones, have not been shown to prevent cardiovascular risk as a byproduct of reducing blood sugar.

In light of this, the FDA is asking all manufacturers of approved oral anti-diabetes drugs to include a statement on their label saying that there is no data that the drugs have the ability to protect the heart.

HealthDay

Product Description

Most important information about Avandia

Pharmacokinetics

Possible Side Effects

More information about AVANDIA (Rosiglitazone):

AVANDIA (Rosiglitazone): What You Should Know

Can Avandia or other drugs prevent diabetes?

Actos beats Avandia in sugar, fat control: study

Avandia approved for combination with insulin in type 2 diabetes treatment

Avandia Reduces Risk of Progresson from Pre-Diabetes to Type 2 Diabetes by 62 percent

EMEA Statement on Recent Publication on Cardiac Safety of Rosiglitazone (Avandia, Avandamet, Avaglim)

GSK Revises US Labeling for Avandia

Data Affirms Avandia (Rosiglitazone maleate) Cardiovascular Safety Profile

Reaction to Avandia Warnings Stronger Among Internists Than Endocrinologists, According to Study by GfK Market Measures

Texas Family Sues GlaxoSmithKline (GSK) Over Man’s Heart Attack Death Following Avandia Use

Older Diabetics Using Avandia Face Increased Death Risk

Diabetes Drug Avandia Could Weaken Bones

Avandia Label to Get Heart-Attack Warning

To buy AVANDIA click HERE: My Family Drugstore