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Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with high-ly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term carcinogenicity studies have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/ kg/ day and 1500 mg/ kg/ day, respectively. These doses are both approximately four times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons. No evidence of carcinogenicity with metformin was found in either male or female mice. Similarly, there was no tumorigenic poten-tial observed with metformin in male rats. There was, however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/ kg/ day. Text Continues Below
There was no evidence of mutagenic potential of metformin in the following in vitro tests: Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test (human lymphocytes). Results in the in vivo mouse micronucleus test were also negative. Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/ kg/ day, which is approximately three times the maximum recommended human daily dose based on body surface area comparisons. Pregnancy Teratogenic Effects: Pregnancy Category B. Recent information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities. Most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Because animal reproduction studies are not always predictive of human response, GLUCOPHAGE and GLUCOPHAGE XR should not be used during pregnancy unless clearly needed. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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