Avandamet - Warnings & Precautions

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Rosiglitazone maleate Cardiac Failure and Other Cardiac Effects:

Rosiglitazone, like other thiazolidinediones, alone or in combination with other antidiabetic agents, can cause fluid retention, which may exacerbate or lead to heart failure. Patients should be observed for signs and symptoms of heart failure.

AVANDAMET should be discontinued if any deterioration in cardiac status occurs. Patients with New York Heart Association (NYHA) Class 3 and 4 cardiac status were not studied during the clinical trials with rosiglitazone maleate. In patients requiring pharmacologic treatment for congestive heart failure, AVANDAMET should not be used (see CONTRAINDICATIONS). In combination with insulin, thiazolidinediones may increase the risk of other cardiovascular adverse events. In three 26-week trials in patients with type 2 diabetes, 216 received 4 mg of rosiglitazone plus insulin, 322 received 8 mg of rosiglitazone plus insulin, and 338 received insulin alone.

These trials included patients with long-standing diabetes and a high prevalence of pre-existing medical conditions, including peripheral neuropathy, retinopathy, ischemic heart disease, vascular disease, and congestive heart failure. In these clinical studies, an increased incidence of edema, cardiac failure, and other cardiovascular adverse events was seen in patients on rosiglitazone and insulin combination therapy compared to insulin and placebo. Patients who experienced cardiovascular events were on average older and had a longer duration of diabetes.

These cardiovascular events were noted at both the 4 mg and 8 mg daily doses of rosiglitazone. In this population, however, it was not possible to determine specific risk factors that could be used to identify all patients at risk of heart failure and other cardiovascular events on combination therapy. Three of 10 patients who developed cardiac failure on combination therapy during the double-blind part of the fixed-dose studies had no known prior evidence of congestive heart failure, or pre-existing cardiac condition.