Avandamet - Side Effects & Drug Interactions

In postmarketing experience with rosiglitazone maleate, adverse events potentially related to volume expansion (e. g., congestive heart failure, pulmonary edema, and pleural effusions) have been reported.

(See also GLUCOPHAGE prescribing information, ADVERSE REACTIONS.)

Laboratory Abnormalities:

Hematologic:

Decreases in mean hemoglobin and hematocrit occurred in a dose-related fashion in patients treated with rosiglitazone maleate (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 rosiglitazone and other hypoglycemic agents or rosiglitazone 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 rosiglitazone. Decreases in hematologic parameters may be related to increased plasma volume observed with rosiglitazone treatment.

In controlled clinical trials of metformin hydrochloride of 29 weeks' duration, a decrease to subnormal levels of previously normal serum vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such a decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of metformin or vitamin B12

supplementation.

Lipids

Changes in serum lipids have been observed following treatment with rosiglitazone maleate (see CLINICAL STUDIES).

Serum Transaminase Levels: In clinical studies in 4,598 patients treated with rosiglitazone maleate 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 rosiglitazone maleate 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 rosiglitazone 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 of exposure of ALT increase to >3X the upper limit of normal was 0.35 for patients treated with rosiglitazone maleate, 0.59 for placebo-treated patients, and 0.78 for patients treated with active comparator agents.