Letraz 2.5 mg FC tablet.

u2022 Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.

u2022 Extended adjuvant treatment of early breast cancer in postmenopausal women who have received prior standard adjuvant tamoxifen therapy.

u2022 First-line treatment in postmenopausal women with hormone-dependent advanced breast cancer.

u2022 Treatment of advanced breast cancer in women with a natural or artificially induced postmenopausal status, who have previously been treated with anti-oestrogen therapy.

u2022 Pre-operative therapy in postmenopausal women with localised hormone receptor-positive breast cancer, to allow subsequent breast-conserving surgery in women not originally considered candidates for this type of surgery. Subsequent treatment after surgery should be in accordance with standard care.

Posology

Adults and elderly patients: The recommended dose of LETRAZ is 2,5 mg once daily by mouth. In the adjuvant and extended adjuvant setting, treatment with LETRAZ is given for 5 years or until tumour relapse occurs, whichever comes first. Where metastatic disease occurs, treatment with LETRAZ should continue until tumour progression is evident.

Method of administration

Oral.

Elderly patients : No dose adjustment is required for geriatric patients.

Paediatric patients : Not suitable for use in children.

Patients with hepatic and/or renal impairment : No dosage adjustment is recommended for patients with mild to moderate hepatic function impairment (Child Pugh grade A and B) or renal function impairment (creatinine clearance u2265 10 ml/min). Insufficient data are available to establish dosage recommendations for patients with a creatinine clearance of < 10 ml/min (see section 4.3). LETRAZ should not be used in patients with severe hepatic impairment (Child-Pugh score C) (see section 4.3).

u2022 Hypersensitivity to the active substance, letrozole, or to any of the excipients, see section 6.1.

u2022 Premenopausal women.

u2022 Pregnancy and lactation.

u2022 Severe hepatic function impairment (Child-Pugh grade C).

u2022 Severe renal function impairment (creatinine clearance < 10 ml/min).

Reductions in bone mineral density can occur during treatment with LETRAZ. This effect may increase the risk of bone fractures, especially in patients with osteoporosis. Patients with or at risk of osteoporosis should have their bone density assessed at the start of therapy and at regular intervals thereafter. Treatment or prophylaxis for osteoporosis should be started as appropriate and carefully monitored.

No data are available in patients with a creatinine clearance of < 10 ml/min (see section 4.3).

An increased incidence of cardiovascular adverse effects has been seen in woman with pre-existing ischaemic heart disease and caution is advised in these patients.

In patient with severe hepatic impairment (Child-Pugh score C), systemic exposure and terminal half-life were approximately doubled compared to healthy volunteers (see section 4.3).

LETRAZ inhibits in vitro the cytochrome P450-isozymes 2A6, and moderately 2C19. CYP2A6 does not play a major role in the metabolism of LETRAZ. However, caution should be used in the concomitant administration of medicines whose disposition is mainly dependent on these isoenzymes and whose therapeutic index is narrow.

The co-administration of LETRAZ with the following commonly prescribed medicines does not result in clinically significant interactions: cimetidine, warfarin, benzodiazepines; barbiturates; NSAIDs such as diclofenac sodium, ibuprofen; paracetamol; furosemide; omeprazole.

Concomitant administration of tamoxifen may reduce plasma concentrations of LETRAZ.

Pregnancy

The use of LETRAZ is contraindicated during pregnancy (see section 4.3).

Breastfeeding

The use of LETRAZ is contraindicated during breastfeeding (see section 4.3).

Fertility

No data is available.

Since fatigue, dizziness and somnolence may occur when using LETRAZ, caution is advised when driving or using machines.

a) Summary of the safety profile

The most frequent side effects with LETRAZ are hot flushes, nausea and fatigue.

b) Tabulated summary of adverse reactions

System Organ Class Frequency Undesirable effect

Infections and infestations Less frequent Urinary tract infections

Neoplasms benign and malignant (including cysts and polyps) Less frequent Tumour pain in metastatic/neoadjuvant setting only

Blood and lymphatic system disorders Less frequent Leukopenia

Immune system disorders Less frequent Anaphylaxis, angioedema

Metabolism and nutrition disorders Frequent Anorexia, appetite increase, hypercholesterolaemia, hypercalcaemia

Less frequent General oedema

Psychiatric disorders Frequent Depression

Less frequent Anxiety, including nervousness and irritability

Nervous system disorders Frequent Headache, dizziness

Less frequent Somnolence, insomnia, memory impairment, dysaesthesia including paraesthesia and hypoaesthesia, taste disturbance, cerebrovascular accident

Eye disorders Less frequent Cataract, eye irritation, blurred vision

Cardiac disorders* Less frequent Palpitations, tachycardia, cardiac failure, angina pectoris, ischaemic cardiac events

Vascular disorders Less frequent Superficial and deep thrombophlebitis including superficial and deep thrombophlebitis, hypertension, pulmonary embolism, arterial thrombosis, cerebrovascular infarction

Respiratory, thoracic and mediastinal disorders Less frequent Dyspnoea, cough

Gastrointestinal disorders Frequent Nausea, vomiting, dyspepsia, constipation, diarrhoea

Less frequent Abdominal pain, stomatitis, dry mouth

Hepato-biliary disorders Less frequent Increased hepatic enzymes, hepatitis

Skin and subcutaneous tissue disorders Frequent Alopecia, increased sweating, rash including erythematous, macupapular, psoriaform and vesicular rash.

Less frequent Pruritus, dry skin, urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme

Musculoskeletal, connective tissue and bone disorders Frequent Arthralgia, myalgia, bone pain, osteoporosis, bone fractures

Less frequent Arthritis, decreased bone mineral density

Renal and urinary disorders Less frequent Increased urinary frequency

Reproductive system and breast disorders Less frequent Vaginal bleeding, vaginal discharge, vaginal dryness, breast pain

General disorders and administrative site conditions Frequent Hot flushes, fatigue, including asthenia and malaise, peripheral oedema

Less frequent Pyrexia, mucosal dryness, thirst

Investigations Frequent Weight increase

Less frequent Weight loss

c) Description of selected adverse reactions

* In the adjuvant setting, irrespective of causality, the following adverse events occurred in the LETRAZ and tamoxifen groups respectively: thromboembolic events, angina pectoris, myocardial infarction and cardiac failure.

Treatment is symptomatic and supportive. There is no specific treatment for overdosage.