|
In monkeys, rosiglitazone (0.6 and 4.6 mg/ kg/ day; approximately 3 and 15 times human AUC at the maximum recommended human daily dose, respectively) diminished the follicular phase rise in serum estradiol with consequential reduction in the luteinizing hormone surge, lower luteal phase progesterone levels, and amenorrhea. The mechanism for these effects appears to be direct inhibition of ovarian steroidogenesis. Animal Toxicology: Heart weights were increased in mice (3 mg/ kg/ day), rats (5 mg/ kg/ day), and dogs (2 mg/ kg/ day) with rosiglitazone treatments (approximately 5, 22, and 2 times human AUC at the maximum recommended human daily dose, respectively). Morphometric measurement indicated that there was hypertrophy in cardiac ventricular tissues, which may be due to increased heart work as a result of plasma volume expansion. Text Continues Below
Pregnancy: Pregnancy Category C: There was no effect on implantation or the embryo with rosiglitazone treatment during early pregnancy in rats, but treatment during mid-late gestation was associated with fetal death and growth retardation in both rats and rabbits. Teratogenicity was not observed at doses up to 3 mg/ kg in rats and 100 mg/ kg in rabbits (approximately 20 and 75 times human AUC at the maximum recommended human daily dose, respectively). Rosiglitazone caused placental pathology in rats (3 mg/ kg/ day). Treatment of rats during gestation through lactation reduced litter size, neonatal viability, and postnatal growth, with growth retardation reversible after puberty. For effects on the placenta, embryo/ fetus, and offspring, the no-effect dose was 0.2 mg/ kg/ day in rats and 15 mg/ kg/ day in rabbits. These no-effect levels are approximately 4 times human AUC at the maximum recommended human daily dose. There are no adequate and well-controlled studies in pregnant women. AVANDIA should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. Because current information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital anomalies as well as increased neonatal morbidity and mortality, most experts recommend that insulin monotherapy be used during pregnancy to maintain blood glucose levels as close to normal as possible. Labor and Delivery The effect of rosiglitazone on labor and delivery in humans is not known. Nursing Mothers Drug-related material was detected in milk from lactating rats. It is not known whether AVANDIA is excreted in human milk. Because many drugs are excreted in human milk, AVANDIA should not be administered to a nursing woman. Page: << Prev | 1 | 2 | 3 | 4 | 5
|
.gif)
