Deerfield, IL, June 6, 2007 – Takeda Pharmaceuticals North America, Inc. (TPNA) today announced that the company will revise warnings related to congestive heart failure (CHF) in the prescribing label of its type 2 diabetes medication ACTOS® (pioglitazone HCl). Takeda is working in conjunction with a request from the U.S. Food and Drug Administration (FDA) that a Boxed Warning be added to the label. The new Boxed Warning will heighten awareness of the risk of CHF.
“By giving the CHF guidance more prominence in the ACTOS label, we hope to ensure that this information is being attended to by treating physicians to optimize patient care,” said Robert Spanheimer, M.D., senior medical director, Diabetes and Metabolism, Takeda Pharmaceuticals North America. “Takeda remains confident in the safety and efficacy of ACTOS when used according to its label, and with this revision, we can heighten patient and physician awareness of an already known, but serious side effect.”
The ACTOS label has always contained information that the thiazolidinedione (TZD) class can cause fluid retention, which may lead to or exacerbate CHF, and Takeda has consistently emphasized the importance of physician education and patient monitoring involved in the use of ACTOS. Through its global system of surveillance, adverse event reports involving patients taking ACTOS are reviewed and reported to the FDA on an ongoing basis.
ACTOS Cardiovascular Safety Data
The ACTOS label was most recently updated in February 2007 to incorporate important cardiovascular safety data from the PROactive Study (PROspective PioglitAzone Clinical Trial In MacroVascular Events), a large outcomes trial. The updated ACTOS label confirmed that ACTOS was not associated with an increase in mortality or in total macrovascular events, including heart attacks and stroke. PROactive demonstrated that ACTOS, in addition to standard of care, has a proven safety profile in patients with type 2 diabetes who are at high risk for cardiovascular events.
PROactive was a prospective, randomized, double-blind, placebo-controlled outcomes study that investigated the effects of ACTOS on total mortality and macrovascular morbidity in 5,238 high-risk patients with type 2 diabetes. Patients were randomized to ACTOS or placebo in addition to diabetes and cardiovascular standard of care, and followed for up to 3.5 years. This landmark study is the first and only macrovascular outcomes trial with any thiazolidinedione (TZD).
While the incidence of serious heart failure (CHF) was higher for ACTOS-treated vs. placebo-treated patients (5.7% vs. 4.1%), there was no increase in the incidence of death subsequent to a report of serious heart failure (1.5% vs. 1.4%, respectively).
The Difference Between Heart Attack Events and CHF
“While physicians recognize the difference between heart failure and heart attacks, there remains significant confusion among patients,” says Dr. Spanheimer.
According to the American Heart Association, CHF is a known complication for people with type 2 diabetes in which inadequate pumping from the heart causes accumulation of fluid throughout the body including the lungs. The heart continues to work, but inefficiently.
Heart attacks, also known as myocardial infarctions, cause permanent damage to the heart muscle. This damage usually occurs when the supply of blood is blocked by plaque buildup due to atherosclerosis.
Cardiovascular disease is a major complication associated with type 2 diabetes. As a result, Takeda has always evaluated the safety and efficacy of ACTOS with a particular emphasis on cardiovascular health, and has conducted a robust clinical trial program in the area. Takeda continues to work with the FDA to educate patients and physicians on the latest data on the cardiovascular effects of ACTOS.
“We are confident in the scientific validity and important safety information from PROactive and that there was no increase in mortality or total macrovascular events with ACTOS,” added Dr. Spanheimer. “This PROactive cardiovascular safety information about heart attacks, in addition to the boxed CHF warning, are important data that will help physicians make the treatment decisions that are best for their patients.”
ACTOS works by directly targeting insulin resistance, a condition in which the body does not efficiently use the insulin it produces to control blood glucose levels. ACTOS is taken once daily as an adjunct to diet and exercise, and is approved for use for type 2 diabetes as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas or metformin.
ACTOS is not for everyone. ACTOS can cause fluid retention that may lead to or worsen heart failure, so tell your doctor if you have a history of these conditions. Talk to your doctor immediately if you experience rapid weight gain, fluid retention, or shortness of breath while taking ACTOS. If you have moderate to severe heart failure, ACTOS is not recommended. Your doctor should perform a blood test to check for liver problems before you start ACTOS and periodically thereafter.
Do not take ACTOS if you have active liver disease. Talk to your doctor immediately if you experience nausea, vomiting, stomach pain, tiredness, loss of appetite, dark urine, or yellowing of the skin. If you are of childbearing age, talk to your doctor before taking ACTOS as it could increase your chance of becoming pregnant. Some people taking ACTOS may experience flu-like symptoms, mild to moderate swelling of legs and ankles, and anemia. When taking ACTOS with insulin or sulfonylureas, you may be at risk for low blood sugar. Patients with diabetes should have regular eye exams. If you experience vision problems, consult your doctor immediately. Very rarely, some patients have experienced visual changes while taking ACTOS.
Please visit the ACTOS Web site at www.actos.com for Complete Prescribing Information.
Takeda Pharmaceuticals North America, Inc.
Based in Deerfield, Ill., Takeda Pharmaceuticals North America, Inc., is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. In the United States, Takeda currently markets oral diabetes, insomnia and gastroenterology treatments, and through the Takeda Global Research & Development Center, Inc., the company has a robust pipeline with compounds in development for diabetes, cardiovascular disease and other conditions. Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. To learn more about the company and its products, visit www.tpna.com .
ACTOS® (pioglitazone HCl) is a registered trademark of Takeda Pharmaceutical Company Limited and used under license by Takeda Pharmaceuticals North America, Inc.
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