ANASTROZOLE Drug Interactions: What You Need to Know

INTERACTIONS

• Tamoxifen: Do not use in combination with anastrozole tablets. No additional benefit seen over tamoxifen monotherapy. ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. )
• Estrogen-containing products: Combination use may diminish activity of Anastrozole Tablets. ( Error! Hyperlink reference not valid. )

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 a 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 Error! Hyperlink reference not valid. ]. 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 a study conducted in 16 male volunteers, anastrozole did not alter the exposure (as measured by Cmax 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 1 mg will affect other drugs as a result of inhibition of cytochrome P450 <span class="opacity-50 text-xs">[see Error! Hyperlink reference not valid. ]</span>.

4 CONTRAINDICATIONS

• Women of premenopausal endocrine status, including pregnant women ( 4.1 , 8.1 )
• Patients with demonstrated hypersensitivity to anastrozole or any excipient ( 4.2 )

4.1 Pregnancy and Premenopausal Women Anastrozole may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Anastrozole is contraindicated in women who are or may become pregnant. There are no adequate and well-controlled studies in pregnant women using anastrozole. If anastrozole is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus or potential risk for loss of the pregnancy <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 )]</span>.

4.2 Hypersensitivity Anastrozole is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. Observed reactions include anaphylaxis, angioedema, and urticaria <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 )]</span>.

AND PRECAUTIONS

• In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events occurred with anastrozole tablets use compared to tamoxifen use. Consider risks and benefits. ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. )
• Decreases in bone mineral density may occur. Consider bone mineral density monitoring. ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. )
• Increases in total cholesterol may occur. Consider cholesterol monitoring. ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. )
• Embryo-Fetal Toxicity: anastrozole tablets may cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. )

5.1 Ischemic Cardiovascular Events In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events was observed with anastrozole in the ATAC trial (17% of patients on anastrozole and 10% of patients on tamoxifen). Consider risk and benefits of anastrozole therapy in patients with pre-existing ischemic heart disease <span class="opacity-50 text-xs">[see Error! Hyperlink reference not valid. ]</span>.

5.2 Bone Effects Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole 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<span class="opacity-50 text-xs">[see Error! Hyperlink reference not valid. ]</span>.

5.3 Cholesterol During the ATAC trial, more patients receiving anastrozole were reported to have elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively) <span class="opacity-50 text-xs">[see Error! Hyperlink reference not valid. ]</span>.

5.4 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, anastrozole 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 and for at least 3 weeks after the last dose [ see Use in Specific Populations ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ) and Error! Hyperlink reference not valid. ].