LETROZOLE

5 mg once daily. No dose adjustment is required for elderly patients. In patients with advanced or metastatic breast cancer, treatment with Letrozole Tablets should continue until tumour progression is evident. In the adjuvant and extended adjuvant setting, treatment with Letrozole Tablets should continue for 5 years or until tumour relapse occurs, whichever is first.

1). In the neoadjuvant setting, treatment with Letrozole tablet could be continued for 4 to 8 months in order to establish optimal tumour reduction. If the response is not adequate, treatment with Letrozole tablet should be discontinued and surgery scheduled and/or further treatment options discussed with the patient.

Paediatric population Letrozole tablet is not recommended for use in children and adolescents. The safety and efficacy of Letrozole tablet in children and adolescents aged up to 17 years have not been established. Limited data are available and no recommendation on a posology can be made.

Renal impairment No dosage adjustment of Letrozole tablet is required for patients with renal insufficiency with creatinine clearance ≥10 ml/min. 2). Hepatic impairment No dose adjustment of Letrozole tablet is required for patients with mild to moderate hepatic insufficiency (Child-Pugh A or B).

Insufficient data are available for patients with severe hepatic impairment. 2). Method of administration Letrozole tablet should be taken orally and can be taken with or without food. The missed dose should be taken as soon as the patient remembers.

However, if it is almost time for the next dose (within 2 or 3 hours), the missed dose should be skipped, and the patient should go back to her regular dosage schedule. 2).

Summary of the safety profile The frequencies of adverse reactions for Letrozole are mainly based on data collected from clinical trials. Up to approximately one third of the patients treated with Letrozole in the metastatic setting and approximately 80% of the patients in the adjuvant setting as well as in the extended adjuvant setting experienced adverse reactions.

The majority of the adverse reactions occurred during the first few weeks of treatment. The most frequently reported adverse reactions in clinical studies were hot flushes, hypercholesterolaemia, arthralgia, fatigue, increased sweating and nausea.

Important additional adverse reactions that may occur with Letrozole are: skeletal events such as osteoporosis and/or bone fractures and cardiovascular events (including cerebrovascular and thromboembolic events). The frequency category for these adverse reactions is described in Table 1.

Tabulated list of adverse reactions The frequencies of adverse reactions for Letrozole are mainly based on data collected from clinical trials. The following adverse drug reactions, listed in Table 1, were reported from clinical studies and from post- marketing experience with Letrozole: Table 1 Adverse reactions are ranked under headings of frequency, the most frequent first, using 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), not known (cannot be estimated from the available data).

Infections and infestations Uncommon:

Urinary tract infection Neoplasms, benign, malignant and unspecified (including cysts and polyps) Uncommon: Tumour pain1 Blood and lymphatic system disorders Uncommon: Leukopenia Immune system disorders Not known: Anaphylactic reaction Metabolism and nutrition disorders Very common: Hypercholesterolaemia Common: Decreased appeti, increased appetite Psychiatric disorders Common: Depression Uncommon: Anxiety (including nervousness), irritability Nervous system disorders Common: Headache, dizziness Uncommon: Somnolence, insomnia, memory impairment, dysaesthesia (including paraesthesia, hypoaesthesia), dysgeusia, cerebrovascular accident, carpal tunnel syndrome Eye disorders Uncommon: Cataract, eye irritation, blurred vision Cardiac disorders Common: Palpitations1 Uncommon: Tachycardia, ischaemic cardiac events(including new or worsening angina, angina requiring surgery, myocardial infarction and myocardial ischaemia) Vascular disorders Very common: Hot flush Common: Hypertension Uncommon: Thrombophlebitis (including superficial and deep vein thrombophlebitis) Rare: Pulmonary embolism, arterial thrombosis, cerebral infarction Respiratory, thoracic and mediastinal disorders Uncommon: Dyspnoea, cough Gastrointestinal disorders Common: Nausea, dyspepsia1, constipation, abdominal pain, diarrhoea, vomiting Uncommon: Dry mouth, stomatitis1 Hepatobiliary disorders Uncommon: Increased hepatic enzymes, hyperbilirubinemia, jaundice Not known: Hepatitis Skin and subcutaneous tissue disorders Very common: Hyperhidrosis Common: Alopecia, rash (including erythematous, maculopapular, psoriaform, and vesicular rash), dry skin Uncommon: Pruritus, urticaria Not known: Angioedema, toxic epidermal necrolysis, erythema multiforme Musculoskeletal and connective tissue disorders Very common: Arthralgia Common: Myalgia, bone pain1, osteoporosis, bone fractures, arthritis Uncommon: Tendonitis Rare: Tendon rupture Not known: Trigger finger Renal and urinary disorders Uncommon: Pollakiuria Reproductive system and breast disorders Common: Vaginal bleeding Uncommon: Vaginal discharge, vulvovaginal dryness, breast pain General disorders and administration site conditions Very common: Fatigue (including asthenia, malaise) Common: Peripheral oedema, chest pain Uncommon: General oedema, mucosal dryness, thirst, pyrexia Investigations Common: Weight increased Uncommon: Weight decreased 1 Adverse drug reactions reported only in the metastatic setting Some adverse reactions have been reported with notably different frequencies in the adjuvant treatment setting.

Menopausal status In patients whose menopausal status is unclear, luteinising hormone (LH), follicle- stimulating hormone (FSH) and/or oestradiol levels should be measured before initiating treatment with Letrozole tablet. Only women of postmenopausal endocrine status should receive Letrozole tablet.

Renal impairment Letrozole Tablets has not been investigated in a sufficient number of patients with a creatinine clearance lower than 10 ml/min. The potential risk/benefit to such patients should be carefully considered before administration of Letrozole.

Hepatic impairment In patients with severe hepatic impairment (Child-Pugh C), systemic exposure and terminal half-life were approximately doubled compared to healthy volunteers. 2). Bone effects Letrozole Tablets is a potent oestrogen-lowering agent.

Women with a history of osteoporosis and/or fractures, or who are at increased risk of osteoporosis, should have their bone mineral density formally assessed prior to the commencement of adjuvant and extended adjuvant treatment and monitored during and following treatment with letrozole.

Treatment or prophylaxis for osteoporosis should be initiated as appropriate and carefully monitored. 1). Tendonitis and tendon rupture Tendonitis and tendon ruptures (rare) may occur. g. 8). 5). This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicinal product also contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium-free”.

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