Anastro-cell Mechanism of Action

Pharmacotherapeutic group: Enzyme inhibitors. ATC Code: L02BG03.
Pharmacological Properties: Pharmacodynamic Properties: Anastrozole is a potent and highly selective non-steroidal aromatase inhibitor. In postmenopausal women, estradiol is produced primarily from the conversion of androstenedione to estrone through the aromatase enzyme complex in peripheral tissues. Estrone is subsequently converted to estradiol. Reducing circulating estradiol levels has been shown to produce a beneficial effect in women with breast cancer. In postmenopausal women, Anastrozole at a daily dose of 1 mg produced estradiol suppression of greater than 80% using a highly sensitive assay method.
Anastrozole does not possess any progestogenic, androgenic or oestrogenic activity.
Daily doses of Anastrozole up to 10 mg do not have any effect on cortisol or aldosterone secretion, measured before or after standard ACTH (adrenocorticotropic hormone) challenge testing. Corticoid supplements are therefore not needed.
Primary adjuvant treatment of early breast cancer: As with all treatment decisions, women with breast cancer and their physician, should assess the relative benefits and risks of the treatment.
When Anastrozole and tamoxifen were co-administered, the efficacy and safety were similar to tamoxifen when given alone, irrespective of hormone receptor status. The exact mechanism of this is not yet clear. It is not believed to be due to a reduction in the degree of estradiol suppression produced by Anastrozole.
Pediatrics: Anastrozole is not indicated for use in children. Efficacy has not been established in the pediatric populations studied (see as follows). The number of children treated was too limited to draw any reliable conclusions on safety. No data on the potential long-term effects of anastrozole treatment in children are available.
Pharmacokinetic Properties: Absorption: Absorption of Anastrozole is rapid and maximum plasma concentrations typically occur within two hours of dosing (under fasted conditions). Food slightly decreases the rate but not the extent of absorption. The small change in the rate of absorption is not expected to result in a clinically significant effect on steady-state plasma concentrations during once daily dosing of Anastrozole tablets. Approximately 90 to 95% of plasma Anastrozole steady-state concentrations are attained after 7 daily doses. There is no evidence of time or dose-dependency of Anastrozole pharmacokinetic parameters.
Distribution: Anastrozole is only 40% bound to plasma proteins.
Elimination: Anastrozole is eliminated slowly with a plasma elimination half-life of 40 to 50 hours.
Metabolism: Anastrozole is extensively metabolised by postmenopausal women with less than 10% of the dose excreted in the urine unchanged within 72 hours of dosing. Metabolism of Anastrozole occurs by N-dealkylation, hydroxylation and glucuronidation. The metabolites are excreted primarily via the urine. Triazole, the major metabolite in plasma, does not inhibit aromatase.
The apparent oral clearance of Anastrozole in volunteers with stable hepatic cirrhosis or renal impairment was in the range observed in healthy volunteers.
Age dependency of pharmacokinetics: Anastrozole pharmacokinetics is independent of age in postmenopausal women.
Pharmacokinetics in children and adolescents: In boys with pubertal gynecomastia, Anastrozole was rapidly absorbed, was widely distributed, and was eliminated slowly with a half-life of approximately 2 days. Clearance of Anastrozole was lower in girls than in boys and exposure higher, Anastrozole in girls was widely distributed and slowly eliminated, with an estimated half-life of approximately 0.8 days.