Brands, Medical Use, Clinical Data
- Antineoplastic Agents
- Aromatase Inhibitors
Brands / Synonyms
Anastrole; Anastrozol; Arimidex; Arimidex
For treatment of breast cancer in post-menopausal women.
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 circulatin estrogen, leading to a decreased tumor mass or delayed progression of tumor growth in some women.
Well absorbed into the systemic cirulation following oral administration. Food does not affect the extent of absorption.
In rats, lethality is greater than 100 mg/kg.
Biotrnasformation / Drug Metabolism
Hepatic. Metabolized mainly by N-dealkylation, hydroxylation, and glucuronidation to inactive metabolites. Primary metabolite is an inactive triazole.
ARIMIDEX is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the
Anastrozole inhibited in vitro metabolic reactions catalyzed by cytochromes P450 1A2, 2C8/9, and 3A4 but
only at relatively high concentrations. Anastrozole did not inhibit P450 2A6 or the polymorphic P450 2D6 in human
liver microsomes. Anastrozole did not alter the pharmacokinetics of antipyrine. Although there have been no formal
interaction studies other than with antipyrine, based on these in vivo and in vitro studies, it is
unlikely that co-administration of a 1 mg dose of ARIMIDEX with other drugs will result in clinically significant
drug inhibition of cytochrome P450-mediated metabolism of the other drugs.
An interaction study with warfarin showed no clinically significant effect of anastrozole on warfarin
pharmacokinetics or anticoagulant activity.
At a median follow-up of 33 months, the combination of ARIMIDEX and tamoxifen did not demonstrate any efficacy
benefit when compared with tamoxifen in all patients as well as in the hormone receptor-positive subpopulation. This
treatment arm was discontinued from the trial. Based on clinical and pharmacokinetic results from the ATAC trial,
tamoxifen should not be administered with anastrozole (see CLINICAL PHARMACOLOGY
ñ Drug Interactions and CLINICAL PHARMACOLOGY - Clinical Studies - Adjuvant
Treatment of Breast Cancer in Postmenopausal Women subsections). Co-administration of anastrozole and tamoxifen
resulted in a reduction of anastrozole plasma levels by 27% compared with those achieved with anastrozole
Estrogen-containing therapies should not be used with ARIMIDEX as they may diminish its pharmacologic action.
Drug/Laboratory Test Interactions
No clinically significant changes in the results of clinical laboratory tests have been observed.