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Hypoglycemia was the most frequently reported adverse event in the fixed-dose insulin combination trials, although few patients withdrew for hypoglycemia (4 of 408 for AVANDIA plus insulin and 1 of 203 for insulin alone). Rates of hypoglycemia, confirmed by capillary blood glucose concentration 50 mg/ dL, were 6% for insulin alone and 12% (4 mg) and 14% (8 mg) for insulin in combination with AVANDIA. Laboratory Abnormalities: Hematologic: Text Continues Below
Decreases in mean hemoglobin and hematocrit occurred in a dose-related fashion in patients treated with AVANDIA (mean decreases in individual studies up to 1.0 gram/ dL hemoglobin and up to 3.3% hematocrit). The time course and magnitude of decreases were similar in patients treated with a combination of AVANDIA and other hypoglycemic agents or AVANDIA monotherapy. Pre-treatment levels of hemoglobin and hematocrit were lower in patients in metformin combination studies and may have contributed to the higher reporting rate of anemia. White blood cell counts also decreased slightly in patients treated with AVANDIA. Decreases in hematologic parameters may be related to increased plasma volume observed with treatment with AVANDIA. Lipids: Changes in serum lipids have been observed following treatment with AVANDIA (see CLINICAL STUDIES). Serum Transaminase Levels: In clinical studies in 4,598 patients treated with AVANDIA encompassing approximately 3,600 patient years of exposure, there was no evidence of drug-induced hepatotoxicity or elevated ALT levels. In controlled trials, 0.2% of patients treated with AVANDIA had reversible elevations in ALT >3X the upper limit of normal compared to 0.2% on placebo and 0.5% on active comparators. Hyperbilirubinemia was found in 0.3% of patients treated with AVANDIA compared with 0.9% treated with placebo and 1% in patients treated with active comparators. In the clinical program including long-term, open-label experience, the rate per 100 patient years exposure of ALT increase to >3X the upper limit of normal was 0.35 for patients treated with AVANDIA, 0.59 for placebo-treated patients, and 0.78 for patients treated with active
comparator agents. In pre-approval clinical trials, there were no cases of idiosyncratic drug reactions leading to hepatic failure. In postmarketing experience with AVANDIA, reports of hepatic enzyme elevations 3 or more times the upper limit of normal and hepatitis have been received (see PRECAUTIONS, General, Hepatic Effects). Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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