Arimidex

Anastrozole is used with other treatments, such as surgery or radiation, to treat early breast cancer in women who have experienced menopause (change of life; end of monthly menstrual periods). This medication is also used in women, who have experienced menopause, as a first treatment of breast cancer that has spread within the breast or to other areas of the body. This medication is also used to treat breast cancer in women whose breast cancer has worsened after taking tamoxifen (Nolvadex). Anastrozole is in a class of medications called nonsteroidal aromatase inhibitors. It works by decreasing the amount of estrogen the body makes. This can slow or stop the growth of many types of breast cancer cells that need estrogen to grow.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Arimidex there are no specific foods that you must exclude from your diet when receiving Arimidex.

Tell your doctor if you are breastfeeding or are planning to breastfeed.

It is not known if Arimidex crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Arimidex.

Take Arimidex exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The recommended dose for Arimidex (anastrozole) 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.

Anastrozole lowers estrogen levels in postmenopausal women, which may slow the growth of certain types of breast tumors that need estrogen to grow in the body.

Anastrozole is used to treat breast cancer in postmenopausal women. It is often given to women whose cancer has progressed even after taking tamoxifen (Nolvadex, Soltamox).

Anastrozole may also be used for purposes not listed in this medication guide.

You should not use this medication if you are allergic to anastrozole, if you are breast-feeding a baby, or if you have not yet completed menopause. Anastrozole is not for use in men or children.

To make sure anastrozole is safe for you, tell your doctor if you have:

• heart disease;

• circulation problems;

• a history of stroke or blood clot;

• severe liver disease;

• high cholesterol; or

• osteoporosis or low bone mineral density.

Anastrozole can decrease bone mineral density, which may increase your risk of developing osteoporosis. Your bone mineral density may need to be tested before and during treatment with anastrozole.

Although it is not likely that a postmenopausal woman would be pregnant, anastrozole could harm an unborn baby. Do not take this medicine if you are pregnant or may become pregnant. Use effective birth control if you are not past menopause, and tell your doctor right away if you become pregnant during treatment.

It is not known whether anastrozole passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using anastrozole.

You may need to take a pregnancy test before using anastrozole, to make sure you are not pregnant.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

In the U.S.

• Arimidex

Available Dosage Forms:

• Tablet

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Aromatase Inhibitor

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Blurred vision
• chest pain or discomfort
• dizziness
• headache
• nervousness
• pounding in the ears
• shortness of breath
• slow or fast heartbeat
• swelling of the feet or lower legs

• Arm, back, or jaw pain
• chest tightness or heaviness
• cough or hoarseness
• difficult or painful urination
• dizziness, severe
• fever or chills
• headache, continuing
• increased blood pressure
• lower back or side pain
• nausea
• pain, tenderness, bluish color, or swelling of the foot or leg
• sore throat
• sudden shortness of breath
• sweating
• unusual tiredness or weakness
• vaginal bleeding (unexpected and heavy)

• Blistering, peeling, or loosening of the skin
• hives
• itching, puffiness, or swelling of the eyelids or around the eyes, face, lips, or tongue
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• red skin lesions, often with a purple center
• sores, ulcers, or white spots in the mouth or on the lips
• welts

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• back pain
• belching
• body aches or pain
• bone pain
• congestion
• constipation
• decrease in height
• diarrhea
• dry mouth
• dryness or soreness of the throat
• feeling of warmth
• fever
• flushing or redness of the skin, especially on the face and neck
• heartburn
• hot flashes
• increased appetite
• indigestion
• lack or loss of strength
• loss of appetite
• mood or mental changes
• pain in the back, ribs, arms, or legs
• pain, general
• pelvic pain
• runny nose
• skin rash
• stomach discomfort, upset, or pain
• tender, swollen glands in the neck
• trouble in swallowing
• voice changes
• vomiting
• weakness
• weight loss

• Anxiety and confusion
• breast pain
• chills
• cough producing mucus
• difficulty breathing
• dryness of the vagina
• general feeling of discomfort or illness
• itching of the skin
• joint pain and stiffness
• loss of hair
• muscle pain
• numbness or tingling of the hands or feet
• shivering
• sleepiness or unusual drowsiness
• trouble sleeping or sleeplessness
• weight gain
• wheezing

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Tell all of your health care providers that you take Arimidex. This includes your doctors, nurses, pharmacists, and dentists.
• Have a bone density test as you have been told by your doctor. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine lowers the estrogen in your body, which may cause your bones to get thinner and weaker. This may raise the chance of broken bones like in the spine, hip, and wrist. Talk with your doctor.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Adjuvant Treatment

Arimidex is indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.

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.

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.

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)].

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)].

The tablets are white, biconvex, film-coated containing 1 mg of anastrozole. The tablets are impressed on one side with a logo consisting of a letter “A” (upper case) with an arrowhead attached to the foot of the extended right leg of the “A” and on the reverse with the tablet strength marking “Adx 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)].

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)].

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)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

A conventional carcinogenesis study in rats at doses of 1.0 to 25 mg/kg/day (about 10 to 243 times the daily maximum recommended human dose on a mg/m2 basis) administered by oral gavage for up to 2 years revealed an increase in the incidence of hepatocellular adenoma and carcinoma and uterine stromal polyps in females and thyroid adenoma in males at the high dose. A dose-related increase was observed in the incidence of ovarian and uterine hyperplasia in females. At 25 mg/kg/day, plasma AUC0-24 hr levels in rats were 110 to 125 times higher than the level exhibited in postmenopausal volunteers at the recommended dose. A separate carcinogenicity study in mice at oral doses of 5 to 50 mg/kg/day (about 24 to 243 times the daily maximum recommended human dose on a mg/m2 basis) for up to 2 years produced an increase in the incidence of benign ovarian stromal, epithelial and granulosa cell tumors at all dose levels. A dose-related increase in the incidence of ovarian hyperplasia was also observed in female mice. These ovarian changes are considered to be rodent-specific effects of aromatase inhibition and are of questionable significance to humans. The incidence of lymphosarcoma was increased in males and females at the high dose. At 50 mg/kg/day, plasma AUC levels in mice were 35 to 40 times higher than the level exhibited in postmenopausal volunteers at the recommended dose.

Arimidex has not been shown to be mutagenic in in vitro tests (Ames and E. coli bacterial tests, CHO-K1 gene mutation assay) or clastogenic either in vitro (chromosome aberrations in human lymphocytes) or in vivo (micronucleus test in rats).

Oral administration of anastrozole to female rats (from 2 weeks before mating to pregnancy day 7) produced significant incidence of infertility and reduced numbers of viable pregnancies at 1 mg/kg/day (about 10 times the recommended human dose on a mg/m2 basis and 9 times higher than the AUC0-24 hr found in postmenopausal volunteers at the recommended dose). Pre-implantation loss of ova or fetus was increased at doses equal to or greater than 0.02 mg/kg/day (about one-fifth the recommended human dose on a mg/m2 basis). Recovery of fertility was observed following a 5-week non-dosing period which followed 3 weeks of dosing. It is not known whether these effects observed in female rats are indicative of impaired fertility in humans.

Multiple-dose studies in rats administered anastrozole for 6 months at doses equal to or greater than 1 mg/kg/day (which produced plasma anastrozole Cssmax and AUC0-24 hr that were 19 and 9 times higher than the respective values found in postmenopausal volunteers at the recommended dose) resulted in hypertrophy of the ovaries and the presence of follicular cysts. In addition, hyperplastic uteri were observed in 6-month studies in female dogs administered doses equal to or greater than 1 mg/kg/day (which produced plasma anastrozole Cssmax and AUC0-24 hr that were 22 times and 16 times higher than the respective values found in postmenopausal women at the recommended dose). It is not known whether these effects on the reproductive organs of animals are associated with impaired fertility in premenopausal women.

Animal Toxicology and/or Pharmacology

Reproductive Toxicology

Anastrozole has been found to cross the placenta following oral administration of 0.1 mg/kg in rats and rabbits (about 1 and 1.9 times the recommended human dose, respectively, on a mg/m2 basis). Studies in both rats and rabbits at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively (about 1 and 1/3, respectively, the recommended human dose on a mg/m2 basis), administered during the period of organogenesis showed that anastrozole increased pregnancy loss (increased pre- and/or post-implantation loss, increased resorption, and decreased numbers of live fetuses); effects were dose related in rats. Placental weights were significantly increased in rats at doses of 0.1 mg/kg/day or more.

Evidence of fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), was observed in rats administered doses of 1 mg/kg/day (which produced plasma anastrozole Cssmax and AUC0-24 hr that were 19 times and 9 times higher than the respective values found in postmenopausal volunteers at the recommended dose). There was no evidence of teratogenicity in rats administered doses up to 1.0 mg/kg/day. In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about 16 times the recommended human dose on a mg/m2 basis); there was no evidence of teratogenicity in rabbits administered 0.2 mg/kg/day (about 3 times the recommended human dose on a mg/m2 basis).