Anazole Mechanism of Action

Pharmacotherapeutic Group: Antineoplastic.
Pharmacology: Toxicology: Mutagenicity: Genetic toxicology studies show that anastrozole is not a mutagen or a clastogen.
Carcinogenicity: A two-year rat oncogenicity study showed an increased incidence of hepatic neoplasms and uterine stromal polyps in females and thyroid adenomas in males at the high dose (25 mg/kg/day) only. These changes occurred at a dose which represents 100-fold greater exposure than occurs at human therapeutic doses, and are considered not to be clinically relevant to the treatment of patients with anastrozole.
A two-year mouse oncogenicity study showed induction of benign ovarian tumors and a disturbance in the incidence of lymphoreticular neoplasms (fewer histiocytic sarcomas in females and more deaths as a result of lymphomas). These changes are considered to be mouse-specific effects of aromatase inhibition and not clinically relevant to the treatment of patients with anastrozole.
Reproductive Toxicology: Oral administration of anastrozole to pregnant rats and rabbits caused no teratogenic effects at doses up to 1 and 0.2 mg/kg/day, respectively. Those effects seen (placental enlargement in rats and pregnancy failure in rabbits) were related to the pharmacology of the compound.
Oral administration of anastrozole to female rats produced a high incidence of infertility at 1 mg/kg/day and increased pre-implantation loss at 0.02 mg/kg/day. These effects were related to the pharmacology of the compound and were completely reversed after a 5-week compound withdrawal period.
The survival of litters born to rats given anastrozole at 0.02 mg/kg/day and above (from day 17 of pregnancy to day 22 post-partum) was compromised. These effects were related to the pharmacological effects of the compound on parturition. There were no adverse effects on behavior of reproductive performance of the first generation offspring attributable to maternal treatment with anastrozole.