ZOLITRAT

Posology The recommended dose of Zolitrat for adults including the elderly is one 1mg 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.

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 Zolitrat should be taken orally.

The following table presents adverse reactions from clinical trials, post-marketing studies or spontaneous reports. Unless specified, the following 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 <1,000), and very rare (<1/10,000).

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 Nervous system disorders Very common Headache Common Somnolence Carpal Tunnel Syndrome* Vascular disorders Very common Hot flushes Gastrointestinal disorders Very common Nausea Common Diarrhoea Vomiting Hepatobiliary disorders Common Increases in alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase Uncommon Increases in gamma-GT and bilirubin Hepatitis Skin and subcutaneous disorders 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 Musculoskeletal and connective tissue disorders Very common Arthralgia/joint stiffness Arthritis Osteoporosis Common Bone pain Uncommon Trigger finger Reproductive system and breast disorders Common Vaginal dryness Vaginal bleeding*** General disorders and administratio n 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.

However, the majority of these events occurred in patients with identifiable risk factors for the development of the condition. 1%) based on the worst value of the point estimate. ***Vaginal bleeding has been reported commonly, mainly in patients with advanced breast cancer during the first few weeks after changing from existing hormonal therapy to treatment with anastrozole.

If bleeding persists, further evaluation should be considered. The table below presents the frequency of pre-specified adverse events in the ATAC study after a median follow-up of 68 months, irrespective of causality, reported in patients receiving trial therapy and up to 14 days after cessation of trial therapy.

6%) Fracture rates of 22 per 1,000 patient-years and 15 per 1,000 patient-years were observed for the anastrozole and tamoxifen groups, respectively, after a median follow-up of 68 months. The observed fracture rate for anastrozole is similar to the range reported in age- matched postmenopausal populations.

3% in patients treated with tamoxifen. It has not been determined whether the rates of fracture and osteoporosis seen in ATAC in patients on anastrozole treatment reflect a protective effect of tamoxifen, a specific effect of anastrozole, or both.

General Zolitrat 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 Zolitrat with LHRH analogues. 1). 8). Women with osteoporosis or at risk of osteoporosis, should have their bone mineral density formally assessed at the commencement of treatment and at regular intervals thereafter.

Treatment or prophylaxis for osteoporosis should be initiated as appropriate and carefully monitored. 8). Hepatic impairment Zolitrat 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 Zolitrat has not been investigated in breast cancer patients with severe renal impairment. 2). 1). Zolitrat should not be used in boys with growth hormone deficiency in addition to growth hormone treatment. 1). since anastrozole reduces estradiol levels, Zolitrat must not be used in girls with growth hormone deficiency in addition to growth hormone treatment.

Long-term safety data in children and adolescents are not available. Hypersensitivity to lactose This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

1.