Brands, Medical Use, Clinical Data
- Antineoplastic Agents
- Aromatase Inhibitors
Brands / Synonyms
Femara; Letrozol; Letrozole [USAN:INN]
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.
Letrozole is an aromatase inhibitor used in the treatment of breast cancer. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue.
Mechanism of Action
Letrozole 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). Letrozole selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis.
Rapidly and completely absorbed. Absorption is not affected by food.
Biotrnasformation / Drug Metabolism
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.
Femara® (letrozole tablets) is contraindicated in patients with known hypersensitivity to Femara or
any of its excipients.
Clinical interaction studies with cimetidine and warfarin indicated that the coadministration of Femara with these
drugs does not result in clinically- significant drug interactions. (See CLINICAL PHARMACOLOGY)
Coadministration of Femara and tamoxifen 20 mg daily resulted in a reduction of letrozole plasma levels by 38% on
average. There is no clinical experience to date on the use of Femara in combination with other anticancer