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Parafollicular cell (thyroid) adenomas were increased in high-dose male rats (p= 0.003) in a 2-year oral carcinogenicity study at doses of 1 and 3.75 mg/ kg body weight. These doses are equivalent to 0.26 and 1 times a 40 mg human daily dose based on surface area, mg/ m 2 . The relevance of this finding to humans is unknown. Alendronate was not genotoxic in the in vitro microbial mutagenesis assay with and without metabolic activation, in an in vitro mammalian cell mutagenesis assay, in an in vitro alkaline elution assay in rat hepatocytes, and in an in vivo chromosomal aberration assay in mice. In an in vitro chromosomal aberration assay in Chinese hamster ovary cells, however, alendronate gave equivocal results. Alendronate had no effect on fertility (male or female) in rats at oral doses up to 5 mg/ kg/ day (1. 3 times a 40 mg human daily dose based on surface area, mg/ m 2 ). Pregnancy Pregnancy Category C: Text Continues Below
Reproduction studies in rats showed decreased postimplantation survival at 2 mg/ kg/ day and decreased body weight gain in normal pups at 1 mg/ kg/ day. Sites of incomplete fetal ossification were statistically significantly increased in rats beginning at 10 mg/ kg/ day in vertebral (cervical, thoracic, and lumbar), skull, and sternebral bones. The above doses ranged from 0.26 times (1 mg/ kg) to 2.6 times (10 mg/ kg) a maximum recommended daily dose of 40 mg (Paget's disease) based on surface area, mg/ m 2 . No similar fetal effects were seen when pregnant rabbits were treated at doses up to 35 mg/ kg/ day (10.3 times a 40 mg human daily dose based on surface area, mg/ m 2 ). Both total and ionized calcium decreased in pregnant rats at 15 mg/ kg/ day (3. 9 times a 40 mg human daily dose based on surface area, mg/ m 2 ) resulting in delays and failures of delivery. Protracted parturition due to maternal hypocalcemia occurred in rats at doses as low as 0.5 mg/ kg/ day (0. 13 times a 40 mg human daily dose based on surface area, mg/ m 2 ) when rats were treated from before mating through gestation. Page: << Prev | 1 | 2 | 3 | 4 | Next >>
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