Avandia - Warnings & Precautions

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Table 6. Weight Changes (kg) From Baseline During Clinical Trials With AVANDIA

Control Group AVANDIA

4 mg

AVANDIA

8 mg

Monotherapy Duration Median

(25 th , 75 th

percentile)

Median

(25 th , 75 th

percentile)

Median

(25 th , 75 th

percentile)

26 weeks placebo -0.9 (-2.8, 0.9) 1.0 (-0.9, 3.6) 3.1 (1.1, 5.8)

52 weeks sulfonylurea 2.0 (0, 4.0) 2.0 (-0.6, 4.0) 2.6 (0, 5.3)

Combination therapy

sulfonylurea 26 weeks sulfonylurea 0 (-1.3, 1.2) 1.8 (0, 3.1) –

metformin 26 weeks metformin -1.4 (-3.2, 0.2) 0.8 (-1.0, 2.6) 2.1 (0, 4.3)

insulin 26 weeks insulin 0.9 (-0.5, 2.7) 4.1 (1.4, 6.3) 5.4 (3.4, 7.3)

Hematologic:

Across all controlled clinical studies, decreases in hemoglobin and hematocrit (mean decreases in individual studies 1.0 gram/ dL and 3.3%, respectively) were observed for AVANDIA alone and in combination with other hypoglycemic agents. The changes occurred primarily during the first 3 months following initiation of therapy with AVANDIA or following a dose increase in AVANDIA. White blood cell counts also decreased slightly in patients treated with AVANDIA. The observed changes may be related to the increased plasma volume observed with treatment with AVANDIA and may be dose related (see ADVERSE REACTIONS, Laboratory Abnormalities, Hematologic).

Ovulation:

Therapy with AVANDIA, like other thiazolidinediones, may result in ovulation in some premenopausal anovulatory women. As a result, these patients may be at an increased risk for pregnancy while taking AVANDIA (see PRECAUTIONS, Pregnancy, Pregnancy Category C). Thus, adequate contraception in premenopausal women should be recommended.

This possible effect has not been specifically investigated in clinical studies so the frequency of this occurrence is not known.

Although hormonal imbalance has been seen in preclinical studies (see PRECAUTIONS, Carcinogenesis, Mutagenesis, Impairment of Fertility), the clinical significance of this finding is not known. If unexpected menstrual dysfunction occurs, the benefits of continued therapy with AVANDIA should be reviewed.