Anastrozole: uses, appearance and warnings

Anastrozole tablets are 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 anastrozole tablets ( 1.3 ) 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.

The tablets are white to off-white, round, film-coated containing 1 mg of anastrozole. The tablets are debossed with "AN" and "1" on one side and plain surface on the other side. 1 mg tablets ( 3 )

Anastrozole Tablets, 1mg are supplied in bottles of 30 tablets (NDC 51991-620-33), bottles of 90 tablets (NDC 51991-620-90) and bottles of 1000 tablets (NDC 51991-620-10) Storage Store at controlled room temperature, 20 to 25°C (68 to 77°F) [see USP].

Patients with demonstrated hypersensitivity to anastrozole tablets or any excipient ( 4 ) Hypersensitivity Anastrozole tablets are 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 [see Adverse Reactions (6.2) ].

In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events occurred with anastrozole tablet 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 (6.1) ]. 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 (6.1) ]. 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 (6.1) ]. 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 (12.1) ] .

Serious adverse reactions with anastrozole tablets occurring in less than 1 in 10,000 patients, are: 1) skin reactions such as lesions, ulcers, or blisters; 2) allergic reactions with swelling of the face, lips, tongue, and/or throat. This may cause difficulty in swallowing and/or breathing; and 3) changes in blood tests of the liver function, including inflammation of the liver with symptoms that may include a general feeling of not being well, with or without jaundice, liver pain or liver swelling [see Adverse Reactions (6.2) ]. Common adverse reactions (occurring with an incidence of ≥10%) in women taking anastrozole tablets included: hot flashes, asthenia, arthritis, pain, arthralgia, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, headache, bone pain, peripheral edema, increased cough, dyspnea, pharyngitis and lymphedema. …

Tamoxifen: Do not use in combination with anastrozole tablets. No additional benefit seen over tamoxifen monotherapy ( 7.1 , 14.1 ) Estrogen-containing products: Combination use may diminish activity of anastrozole tablets ( 7.2 ) 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 tablets 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) ]. …