| Indication | For adjuvant treatment of hormone receptor positive breast cancer , as well as hormonal treatment of advanced breast cancer in post-menopausal women. Has also been used to treat pubertal gynecomastia and McCune-Albright syndrome; however, manufacturer states that efficacy for these indications have not been established. |
| Pharmacodynamics | Anastrozole is a potent and selective non-steroidal aromatase inhibitor indicated for the treatment of advanced breast cancer in post-menopausal women with disease progression following tamoxifen therapy. Many breast cancers have estrogen receptors and growth of these tumors can be stimulated by estrogens. In post-menopausal women, the principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues, such as adipose tissue, with further conversion of estrone to estradiol. Many breast cancers also contain aromatase; the importance of tumor-generated estrogens is uncertain. Treatment of breast cancer has included efforts to decrease estrogen levels by ovariectomy premenopausally and by use of anti-estrogens and progestational agents both pre- and post-menopausally, and these interventions lead to decreased tumor mass or delayed progression of tumor growth in some women. Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone. |
| Mechanism of action | Anastrozole selectively inhibits aromatase. The principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues. Therefore, aromatase inhibition leads to a decrease in serum and tumor concentration of estrogen, leading to a decreased tumor mass or delayed progression of tumor growth in some women. Anastrozole has no detectable effect on synthesis of adrenal corticosteroids, aldosterone, and thyroid hormone. |
| Absorption | Rapidly absorbed into the systemic cirulation following oral administration. Peak plasma concentrations are usually attained within 2 hours under fasting conditions, with steady-state plasma concentrations attained in approximately 7 days. |
| Volume of distribution | Not Available |
| Protein binding | 40% |
| Metabolism | Hepatic. Metabolized mainly by N-dealkylation, hydroxylation, and glucuronidation to inactive metabolites. Primary metabolite is an inactive triazole. |
| Route of elimination | Hepatic metabolism accounts for approximately 85% of anastrozole elimination. Renal elimination accounts for approximately 10% of total clearance. |
| Half life | 50 hours |
| Clearance | Not Available |
| Toxicity | In rats, lethality is greater than 100 mg/kg. |