Anastrozole

ARIMIDEX is an aromatase inhibitor indicated for: • Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. • First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer. • 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

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 a selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone.

One 1 mg tablet taken once daily 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. No dosage adjustment is necessary for patients with renal impairment or for elderly patients.

Hypersensitivity ARIMIDEX 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. Patients with demonstrated hypersensitivity to ARIMIDEX or any excipient

• 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. • Decreases in bone mineral density may occur. Consider bone mineral density monitoring. • Increases in total cholesterol may occur. Consider cholesterol monitoring. • Embryo-Fetal Toxicity: ARIMIDEX may cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Serious adverse reactions with ARIMIDEX 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. Common adverse reactions (occurring with an incidence of ≥10%) in women taking ARIMIDEX 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 ARIMIDEX. No additional benefit seen over tamoxifen monotherapy. • Estrogen-containing products: Combination use may diminish activity of ARIMIDEX.

Storage Store at controlled room temperature, 20 to 25°C (68 to 77°F).