Anastrozole - Warnings and Precautions

WARNINGS AND PRECAUTIONS In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events occurred with anastrozole 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: anastrozole tablets 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 anastrozole tablets in the ATAC trial (17% of patients on anastrozole tablets and 10% of patients on tamoxifen).

Consider risk and benefits of anastrozole tablets therapy in patients with pre-existing ischemic heart disease [see Adverse Reactions ].

5.2 Bone Effects Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole tablets 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 anastrozole tablets [see Adverse Reactions ].

5.3 Cholesterol During the ATAC trial, more patients receiving anastrozole tablets were reported to have elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively) [see Adverse Reactions ].

5.4 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, anastrozole tablets 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 anastrozole tablets and for at least 3 weeks after the last dose [see Use in Specific Populations ( 8.1, 8.3 ) and Clinical Pharmacology ]