Actos - Warnings & Precautions

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Hypoglycemia:

Patients receiving ACTOS in combination with insulin or oral hypoglycemic agents may be at risk for hypoglycemia, and a reduction in the dose of the concomitant agent may be necessary.

Cardiovascular:

In U. S. placebo-controlled clinical trials that excluded patients with New York Heart Association (NYHA) Class III and IV cardiac status, the incidence of serious car-diac adverse events related to volume expansion was not increased in patients treated with ACTOS as monotherapy or in combination with sulfonylureas or metformin vs. placebo-treated patients. In insulin combination studies, a small number of patients with a history of previously existing cardiac disease developed congestive heart failure when treated with ACTOS in combination with insulin (see WARNINGS). Patients with NYHA Class III and IV cardiac status were not studied in ACTOS clinical trials. ACTOS is not indicated in patients with NYHA Class III or IV cardiac status. In postmarketing experience with ACTOS, cases of congestive heart failure have been reported in patients both with and without previously known heart disease.

Edema:

ACTOS should be used with caution in patients with edema. In all U. S. clinical trials, edema was reported more frequently in patients treated with ACTOS than in placebo-treated patients (see ADVERSE REACTIONS). In postmarketing experience, reports of initiation or worsening of edema have been received.

Weight Gain:

Dose related weight gain was seen with ACTOS alone and in combination with other hypoglycemic agents (Table 6). The mechanism of weight gain is unclear but probably involves a combination of fluid retention and fat accumulation.

Table 6 Weight Changes (kg) from Baseline during Double-Blind Clinical Trials with ACTOS Control Group ACTOS ACTOS ACTOS (Placebo) 15 mg 30 mg 45 mg

Median Median Median Median (25 th /75 th (25 th /75 th (25 th /75 th (25 th /75 th percentile) percentile) percentile) percentile)

Monotherapy -1.4 (-2.7/ 0.0) 0.9 (-0.5/ 3.4) 1.0 (-0.9/ 3.4) 2.6 (0.2/ 5.4) n= 256 n= 79 n= 188 n= 79