GlaxoSmithKline believes there is no liver safety issue with Avandia (rosiglitazone maleate)

Oct 31 2008

GlaxoSmithKline today issued the following response to a petition filed by Public Citizen to the U.S. Food and Drug Administration (FDA) on Avandia (rosiglitazone maleate), a highly effective therapy for treating type 2 diabetes when used in the appropriate patient population.

The safety of patients using our medicine is very important to us. On a continual basis, an external Hepatic Safety Board reviews any adverse event report received by GSK of liver failure, liver-related deaths and liver transplants for possible relationship to Avandia. As recently as July 2008, this panel of experts continued to endorse a favorable hepatic safety profile for Avandia.

Patients being treated with Avandia or other medicines to control blood sugar levels should remain on therapy, unless their doctor advises a different course of action.

Avandia has been shown to be a safe and highly effective treatment for type 2 diabetes for the appropriate patient. GSK strongly supports the safety and efficacy of Avandia based on extensive clinical trial experience and widespread post-marketing use. The record of safety and effectiveness of Avandia is backed by one of the largest clinical trial programs (including 52,000 patients) ever undertaken for any medicine.

Data from long-term clinical trials, which offer the most rigorous scientific measurement of safety and efficacy, provide substantial evidence to assess the benefit-risk of Avandia in treating patients with diabetes. Importantly, the Public Citizen petition did not include data from the current Prescribing Information for Avandia regarding ADOPT (A Diabetes Outcomes Progression Trial). ADOPT, the largest head-to-head diabetes trial, showed that Avandia sustained glycemic control longer than metformin or sulfonylurea, for up to five years. Additionally, outcomes from five long-term clinical studies did not demonstrate an increased risk of total mortality for Avandia compared to other commonly used oral diabetes medicines on the market. The current FDA-approved label for Avandia states that the available data are inconclusive on the risk of myocardial ischemia.

Important Safety Information about Avandia (rosiglitazone maleate)

Prescription Avandia, along with diet and exercise, helps improve blood sugar control in adults with type 2 diabetes. Taking Avandia with insulin or nitrates is not recommended.

Avandia can cause or worsen heart failure. If you have severe heart failure (very poor pumping ability of the heart) you cannot be started on Avandia. Avandia is also not recommended if you have heart failure with symptoms (such as shortness of breath or swelling) even if these symptoms are not severe.

Avandia may increase your risk of other heart problems that occur when there is reduced blood flow to the heart, such as chest pain (angina) or heart attack (myocardial infarction). This risk appeared higher in patients taking medicines called nitrates or insulin.

If you have chest pain or a feeling of chest pressure, you should seek immediate medical attention, regardless of what diabetes medicines you are taking. If you take Avandia tell your doctor right away if you: have swollen legs or ankles, a rapid increase in weight or difficulty breathing, or unusual tiredness; experience changes in vision; become pregnant.

Before taking Avandia, review your medical history and tell your doctor if you:

• Have heart failure or other heart problems, or are on any medicines for high blood pressure, high cholesterol or heart failure, or for prevention of heart disease or stroke.
• Take insulin or nitrate medicines.
• Have a type of diabetic eye disease called macular edema.
• Have liver problems or had liver problems while taking REZULIN (troglitazone).
• Are pregnant or planning to become pregnant.
• Are breastfeeding or planning to breastfeed.

Women taking Avandia should know that Avandia may increase the risk of pregnancy. More fractures have been observed in women taking Avandia. Other possible side effects of Avandia include anemia and hypoglycemia. Your doctor should do blood tests to check your liver before you start Avandia and during treatment as needed.

For more information about Avandia, please see Medication Guide. For further information on Avandia, please see full Prescribing Information at www.avandia.com.