ARIMIDEX

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE ARIMIDEX is an aromatase inhibitor indicated for: • Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer ( 1.1 ) • First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer ( 1.2 ) • 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 ARIMIDEX ( 1.3 ) 1.1 Adjuvant Treatment ARIMIDEX is indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. 1.2 First-Line Treatment ARIMIDEX is 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 ARIMIDEX is 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 ARIMIDEX. Dosage and administration 2 DOSAGE AND ADMINISTRATION One 1 mg tablet taken once daily ( 2.1 ) 2.1 Recommended Dose The dose of ARIMIDEX is one 1 mg tablet taken once a day. For patients with advanced breast cancer, ARIMIDEX should be continued until tumor progression. ARIMIDEX 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, ARIMIDEX 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 ( 8.6 )] . 2.2 Patients with Hepatic Impairment No changes in dose are recommended for patients with mild-to-moderate hepatic impairment. ARIMIDEX has not been studied in patients with severe hepatic impairment [see Use in Specific Populations ( 8.7 )] . Warnings and cautions 5 WARNINGS AND PRECAUTIONS • In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events occurred with ARIMIDEX use compared to tamoxifen use. Consider risks and benefits. ( 5.1 , 6.1 ) • Decreases in bone mineral density may occur. Consider bone mineral density monitoring. ( 5.2 , 6.1 ) • Increases in total cholesterol may occur. Consider cholesterol monitoring. ( 5.3 , 6.1 ) • Embryo-Fetal Toxicity: ARIMIDEX may cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.4 , 8.1 ) 5.1 Ischemic Cardiovascular Events In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events was observed with ARIMIDEX in the ATAC trial (17% of patients on ARIMIDEX and 10% of patients on tamoxifen). Consider risk and benefits of ARIMIDEX therapy in patients with pre-existing ischemic heart disease [see Adverse Reactions ( 6.1 )] . 5.2 Bone Effects Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving ARIMIDEX had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline. Consider bone mineral density monitoring in patients treated with ARIMIDEX [see Adverse Reactions ( 6.1 )] . 5.3 Cholesterol During the ATAC trial, more patients receiving ARIMIDEX were reported to have elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively) [see Adverse Reactions ( 6.1 )] . 5.4 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, ARIMIDEX can cause fetal harm when administered to a pregnant woman. Anastrozole caused embryo-fetal toxicities in rats at maternal exposure that were 9 times the human clinical exposure, based on area under the curve (AUC). In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m 2 basis. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during therapy with ARIMIDEX and for at least 3 weeks after the last dose [see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology ( 12.1 )] . Drug interactions 7 DRUG INTERACTIONS • Tamoxifen: Do not use in combination with ARIMIDEX. No additional benefit seen over tamoxifen monotherapy. ( 7.1 , 14.1 ) • Estrogen-containing products: Combination use may diminish activity of ARIMIDEX. ( 7.2 ) 7.1 Tamoxifen Co-administration of anastrozole and tamoxifen in breast cancer patients reduced anastrozole plasma concentration by 27%. Ho