DESCRIPTION
Anastrozole tablets for oral administration contain mg of anastrozole, non-steroidal aromatase inhibitor. It is chemically described as 1,3-Benzenediacetonitrile, a, a, a?, a?-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl). Its molecular formula is 17 19 5
Mechanism of Action
The growth of many cancers of the breast is stimulated or maintained by estrogens.
In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme.
Anastrozole is selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone.
INDICATIONS AND USAGE
1.1 Adjuvant Treatment
Anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.
1.2 First-Line Treatment
Anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.
1.3 Second-Line Treatment
Anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dose
The dose of anastrozole tablet is one mg tablet taken once day. For patients with advanced breast cancer, anastrozole tablets should be continued until tumor progression. Anastrozole tablets can be taken with or without food.
For adjuvant treatment of early breast cancer in postmenopausal women, the optimal duration of therapy is unknown. In the ATAC trial, anastrozole was administered for five years [see Clinical Studies 14.1)].
No dosage adjustment is necessary for patients with renal impairment or for elderly patients [see Use in Specific Populations
DOSAGE FORMS AND STRENGTHS
The tablets are white to off-white, round biconvex, film coated tablets, with ???AHI??? debossing on one side and plain on other side.
DRUG INTERACTIONS
7.1 Tamoxifen
Co-administration of anastrozole and tamoxifen in breast cancer patients reduced anastrozole plasma concentration by 27%. However, the co-administration of anastrozole and tamoxifen did not affect the pharmacokinetics of tamoxifen or N-desmethyltamoxifen. At median follow-up of 33 months, the combination of anastrozole 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. [see Clinical Studies 14.1)] Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole.
7.2 Estrogen
Estrogen-containing therapies should not be used with anastrozole as they may diminish its pharmacological action.
7.3 Warfarin
In study conducted in 16 male volunteers, anastrozole did not alter the exposure (as measured by max and AUC), and anticoagulant activity (as measured by prothrombin time, activated partial thromboplastin time, and thrombin time) of both R- and S-warfarin.
7.4 Cytochrome P450
Based on in vitro and in vivo results, it is unlikely that co-administration of anastrozole mg will affect other drugs as result of inhibition of cytochrome P450
Pregnancy
PREGNANCY CATEGORY X
