For the extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy. Also for first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer. Also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
Femara Mechanism Of Action:
Femara is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens. In adult nontumor- and tumorbearing female animals, letrozole is as effective as ovariectomy in reducing uterine weight, elevating serum Leuteinizing hormone (LH), and causing the regression of estrogen-dependent tumors. In contrast to ovariectomy, treatment with letrozole does not lead to an increase in serum (folicile stimulating hormone (FSH). Femara selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis.
Primarily hepatic via CYP3A4 and CYP2A6. Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues. It is metabolized slowly to an inactive metabolite whose glucuronide conjugate is excreted renally, representing the major clearance pathway.