Femara 2, 5 mg FC tablets

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

u2022 Extended adjuvant treatment of early invasive breast cancer in post-menopausal women who have received prior standard adjuvant tamoxifen therapy for five years.

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

u2022 Advanced breast cancer after relapse or disease progression, in women with natural or artificially induced postmenopausal endocrine status, who have previously been treated with anti-oestrogens.

u2022 Neo-adjuvant treatment of postmenopausal women with hormone receptor positive, HER-2 negative breast cancer where chemotherapy is not suitable and immediate surgery is not indicated.

FEMARA is not indicated in hormone receptor negative disease.

Posology

Adults

The recommended dose of FEMARA is 2,5 mg once daily. In the adjuvant and extended adjuvant setting, treatment with FEMARA should continue for 5 years or until disease relapse/recurrence occurs, whichever comes first. In patients with metastatic disease, treatment with FEMARA should continue until tumour progression is evident. In the neoadjuvant (preoperative) setting, treatment with FEMARA should be continued for 4 to 8 months in order to establish optimal tumour reduction. If the response is not adequate, treatment with FEMARA should be discontinued, surgery scheduled and/or further treatment options discussed with the patient.

Special Populations

Elderly patients (age 65 years and over): No dose adjustment is required for elderly patients.

Renal impairment: No dosage adjustment of FEMARA is required for patients with renal insufficiency with creatinine clearance (CLcr) u2265 10 mL/min. Insufficient data are available to establish dosage recommendations for patients with a creatinine clearance of u2264 10 mL/min (see sections 4.4 and 5.2).

Hepatic impairment: No dose adjustment of FEMARA is required for patients with mild to moderate hepatic impairment (Child Pugh score A and B). Insufficient data are available for patients with severe hepatic impairment (Child Pugh score C) and should be kept under close supervision (see section 4.4).

Paediatric population: FEMARA is not recommended for the use in children and adolescents. The safety and efficacy in children and adolescents aged up to 17 years have not been established. Limited data are available.

Method of administration

FEMARA should be taken orally and can be taken with or without food. A missed dose should be taken as soon as the patient remembers. However, if it is almost time for the next dose, the missed dose should be skipped, and the patient should go back to their regular dosage schedule. Doses should not be doubled, because with daily doses over 2,5 mg recommended dose, over-proportionality in systemic exposure was observed (see section 5.2).

u2022 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

u2022 Premenopausal endocrine status, pregnancy or lactation.

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

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

Renal impairment

FEMARA 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 FEMARA (see sections 4.3 and 5.2).

Hepatic impairment

In patients with severe hepatic impairment (Child-Pugh C), systemic exposure and terminal half-life were approximately doubled compared to healthy volunteers. Such patients should therefore be kept under close supervision (see sections 4.3 and 5.2).

Bone effects

Osteoporosis and/or bone fractures have been reported with the use of FEMARA. Therefore, monitoring of overall bone health is recommended during treatment.

Tendon disorders

The use of third generation aromatase inhibitors, including letrozole, were found to be associated with tendonitis and tenosynovitis in randomised controlled trials. Tendon rupture was found to be a potential risk. Tendonitis and tenosynovitis were estimated to be of uncommon occurrence, and tendon rupture of rare occurrence. Monitor patients for signs and symptoms of tendon disorders during treatment with FEMARA.

Menopausal status

In patients whose menopausal status is unclear, luteinising hormone (LH), follicle u2013 stimulating hormone (FSH) and/or oestradiol levels should be measured before initiating treatment with FEMARA. Only women of confirmed postmenopausal endocrine status should receive FEMARA.

Co-administration of FEMARA with tamoxifen, other anti-oestrogens or oestrogen-containing therapies should be avoided as these substances may diminish the pharmacological action of FEMARA (see section 4.5).

Contains lactose

Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take FEMARA.

Women of childbearing potential / Contraception in males and females

FEMARA should only be used in women with a clearly established postmenopausal status. The doctor needs to discuss the necessity of adequate contraception with women who have the potential to become pregnant including women who are perimenopausal or who recently became postmenopausal, until their postmenopausal status is fully established.

Pregnancy

FEMARA is contra-indicated during pregnancy. FEMARA may cause foetal harm when administered to a pregnant woman. The patient should be apprised of the potential risk to the foetus, if FEMARA is used during pregnancy or if the patient becomes pregnant while taking this medicine. There are no clinical trials conducted in pregnant women with FEMARA. There have been post-marketing reports of spontaneous abortions and congenital anomalies in infants of mothers who have taken FEMARA (see section 4.3). Cases of birth defects (labial fusion, ambiguous genitalia) have been reported in infants born to woman exposed to off label use (infertility treatment, ovulation induction) of FEMARA during pregnancy.

Lactation

FEMARA is contraindicated during lactation (see section 4.3). It is not known if FEMARA is excreted in human milk. There are no data on the effects of FEMARA on the breastfed child or the effects of FEMARA on milk production.

Fatigue, dizziness and somnolence have been observed with the use of FEMARA. Patients should be advised that their physical and/or mental abilities required for operating machinery or driving a car may be impaired.

Summary of the safety profile: FEMARA was generally well tolerated across all studies as first-line and second-line treatment for advanced breast cancer, as adjuvant treatment of early breast cancer and as extended adjuvant treatment in women who have received prior standard tamoxifen therapy. Approximately one third of the patients treated with FEMARA in the metastatic and neoadjuvant settings, approximately 70-75 % of the patients in the adjuvant setting (both FEMARA and tamoxifen arms), and approximately 80 % of the patients in the extended adjuvant setting (both FEMARA and placebo arms) can be expected to experience adverse reactions. The most frequently reported adverse reactions in the clinical studies were hot flushes, hypercholesterolaemia, arthralgia, fatigue, increased sweating and nausea. Many adverse reactions can be attributed to the normal pharmacological consequences of oestrogen deprivation (e.g. hot flushes, alopecia and vaginal bleeding). Other important additional adverse reactions that may occur with FEMARA are cardiovascular events (including cerebrovascular and thromboembolic events). The following adverse events, not reported in the advanced or metastatic clinical trials, were noted in the extended adjuvant setting arthralgia/arthritis, osteoporosis and bone fractures.

The following adverse drug reactions, listed in Table 1, were reported from clinical studies and from post marketing experience with FEMARA.

Tabulated summary of adverse drug reactions from clinical trials and from post marketing experience with FEMARA

Table 1 Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: very common u226510 %; common u22651 % to <10 %; uncommon u2265 0, 1 % to <1 %; rare u2265 0, 01 % to <0, 1 %; very rare <0, 01 %, including not known/cannot be estimated and isolated reports.

No specific treatment for overdosage is known; treatment should be symptomatic and supportive.