Actos - Warnings & Precautions

WARNINGS

Cardiac Failure and Other Cardiac Effects

ACTOS, like other thiazolidinediones, can cause fluid retention when used alone or in com-bination with other antidiabetic agents, including insulin. Fluid retention may lead to or exacerbate heart failure. Patients should be observed for signs and symptoms of heart fail-ure (see Information for Patients). ACTOS should be discontinued if any deterioration in cardiac status occurs.

Patients with New York Heart Association (NYHA) Class III and IV cardiac status were not studied during clinical trials; therefore, ACTOS is not recommended in these patients (see PRECAUTIONS, Cardiovascular). In one 16-week U. S. double-blind, placebo-controlled clinical trial involving 566 patients with type 2 diabetes, ACTOS at doses of 15 mg and 30 mg in combination with insulin was compared to insulin therapy alone. This trial included patients with long-standing diabetes and a high prevalence of pre-existing medical conditions as follows:

arterial hypertension (57.2%),

peripheral neuropathy (22.6%),

coronary heart disease (19.6%),

retinopathy (13.1%), myocardial infarction (8.8%),

vascular disease (6.4%),

angina pectoris (4.4%),

stroke and/ or transient ischemic attack (4.1%),

congestive heart failure (2.3%).

In this study two of the 191 patients receiving 15 mg ACTOS plus insulin (1.1%) and two of the 188 patients receiving 30 mg ACTOS plus insulin (1.1%) developed congestive heart failure compared with none of the 187 patients on insulin therapy alone. All four of these patients had previous histories of cardiovascular conditions including coronary artery disease, previous CABG procedures, and myocardial infarction. Analysis of data from this study did not identify specific factors that predict increased risk of congestive heart failure on combination therapy with insulin.

PRECAUTIONS

General

ACTOS exerts its antihyperglycemic effect only in the presence of insulin. Therefore, ACTOS should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.