ANASTROZOLE

Posology The recommended dose of anastrozole for adults including the elderly is one 1 mg tablet once a day. For postmenopausal women with hormone receptor-positive early invasive breast cancer, the recommended duration of adjuvant endocrine treatment is 5 years.

For the primary prevention of breast cancer in postmenopausal women at moderate or high risk, the treatment duration is 5 years. Anastrozole treatment for the primary prevention of breast cancer should only be initiated by a medical practitioner experienced in prescribing for this indication, and as part of a shared care pathway arrangement, with appropriate patient identification, management and follow up.

Before commencing treatment, an assessment of the potential benefits and risks is essential, including calculating a patient's risk of developing breast cancer according to local guidelines and risk assessment tools. Validated algorithms are available that calculate breast cancer risk based on features such as age, family history, genetic factors, reproductive factors and history of breast disease.

The use of anastrozole should be as part of a program including regularbreast surveillance tailored to the individual woman, taking into account her risk of breast cancer. 1). Renal impairment No dose change is recommended in patients with mild or moderate renal impairment.

2). Hepatic impairment No dose change is recommended in patients with mild hepatic disease. 4). Method of administration Anastrozole film-coated tablets should be taken orally.

Table 1 presents adverse reactions from clinical trials, post-marketing studies or spontaneous reports. Unless specified, the frequency categories were calculated from the number of adverse events reported in a large phase III study conducted in 9,366 postmenopausal women with operable breast cancer given adjuvant treatment for five years (the Arimidex, Tamoxifen, Alone or in Combination [ATAC] study).

Adverse reactions listed below are classified according to frequency and System Organ Class (SOC). Frequency groupings are defined according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).

The most frequently reported adverse reactions were headache, hot flushes, nausea, rash, arthralgia, joint stiffness, arthritis, and asthenia. Table 1. Adverse reactions by System Organ Class and frequency Adverse reactions by SOC and frequency Metabolism and nutrition disorders Common Anorexia Hypercholesterolaemia Uncommon Hypercalcaemia (with or without an increase in parathyroid hormone) Psychiatric disorders Very common Depression Very common Headache Common Somnolence Carpal Tunnel Syndrome* Sensory disturbances (including paraesthesia, taste loss and taste perversion) Nervous system disorders Not known Memory impairment Eye disorders Not known Dry eye Vascular disorders Very common Hot flushes Very common NauseaGastrointestinal disorders Common Diarrhoea Vomiting Common Increases in alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase Hepatobiliary disorders Uncommon Increases in gamma-GT and bilirubin Hepatitis Very common Rash Common Hair thinning (alopecia) Allergic reactions Uncommon Urticaria Rare Erythema multiforme Anaphylactoid reaction Cutaneous vasculitis (including some reports of Henoch-Schönlein purpura)** Very rare Stevens-Johnson syndrome Angioedema Skin and subcutaneous tissue disorders Not known Lichenoid eruption Very common Arthralgia/joint stiffness Arthritis Osteoporosis Common Bone pain Myalgia Uncommon Trigger finger Musculoskeletal and connective tissue disorders Not known Tendonitis Tendon rupture Reproductive system and breast disorders Common Vaginal dryness Vaginal bleeding *** General disorders and administration site conditions Very common Asthenia * Events of Carpal Tunnel Syndrome have been reported in patients receiving anastrozole treatment in clinical trials in greater numbers than those receiving treatment with tamoxifen.

General Anastrozole should not be used in premenopausal women. The menopause should be defined biochemically (luteinizing hormone [LH], follicle-stimulating hormone [FSH], and/or estradiol levels) in any patient where there is doubt about menopausal status.

There are no data to support the use of anastrozole with LHRH analogues. 1). In the IBIS-II primary prevention study, due to the limited number of women with a confirmed BRCA1 or 2 mutation, there is uncertainty about the absolute benefit in these patients treated with anastrozole for primary prevention of breast cancer.

Higher proportions of women had hypertension (including essential hypertension, hypertension, accelerated hypertension, malignant hypertension and systolic hypertension), hypercholesterolaemia (including hypercholesterolaemia, hyperlipidaemia and blood cholesterol increased) and cardiovascular events when treated with anastrozole rather than with the placebo in the IBIS-II study.

Such cardiovascular risks must be considered when starting anastrozole for primary prevention in healthy individuals as well as a potential cause of new onset/deterioration of these conditions in those already receiving treatment with anastrozole.

8). Women with osteoporosis or osteopenia, or at risk of osteoporosis or osteopenia, should have their bone mineral density formally assessed at the commencement of treatment and at regular intervals thereafter. Treatment or prophylaxis for osteoporosis or osteopenia should be initiated as appropriate and carefully monitored, as per local guidelines.

8). 0, or more than two vertebral fractures are not suitable for anastrozole use in primary prevention. Hepatic impairment Anastrozole has not been investigated in breast cancer patients with moderate or severe hepatic impairment. 2).

Treatment should be based on a benefit-risk evaluation for the individual patient. Renal impairment Anastrozole has not been investigated in breast cancer patients with severe renal impairment. 2). 1). Anastrozole should not be used in boys with growth hormone deficiency in addition to growth hormone treatment.

Anastrozole is contraindicated in:

Pregnant or breast-feeding women. 1.