Femara

/ Novartis

Adult and elderly patients: The recommended dose of Letrozole is 2.5 mg once daily. No dose adjustment is required for elderly patients. In patients with advanced or metastatic breast cancer, treatment with Letrozole should continue until tumour progression is evident. In the adjuvant and extended adjuvant setting, treatment with Letrozole should continue for 5 years or until tumour relapse occurs, whichever is first.
Paediatric population: Letrozole is not recommended for use in children and adolescents. The safety and efficacy of Letrozole 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 is required for patients with renal insufficiency with creatinine clearance ≥10 ml/min. Insufficient data are available in cases of renal insufficiency with creatinine clearance lower than 10 ml/min.
Hepatic impairment: No dose adjustment of Letrozole 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. Patients with severe hepatic impairment (Child-Pugh C) require close supervision. Method of administration: Letrozole  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 (within 2 or 3 hours), the missed dose should be skipped, and the patient should go back to her regular dosage schedule. Doses should not be doubled because with daily doses over the 2.5 mg recommended dose, over-proportionality in systemic exposure was observed.

Femara (letrozole tablets) is indicated for first-line treatment in postmenopausal women with hormone receptor positive or in whom hormone receptor status cannot be determined locally advanced or metastatic breast cancer.
Femara is also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
Extended adjuvant treatment of early breast cancer in postmenopausal women who have received prior standard adjuvant tamoxifen therapy.
Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.

Hypersensitivity to the active substance or to any of the excipients. Premenopausal endocrine status. Pregnancy. Breast-feeding.

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 Femara. Only women of postmenopausal endocrine status should receive Letrozole.
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 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. Such patients should therefore be kept under close supervision.
Bone effects: Letrozole 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.
Tendonitis and tendon rupture: Tendonitis and tendon ruptures (rare) may occur. Close monitoring of the patients and appropriate measures (e.g. immobilisation) must be initiated for the affected tendon.
Other warnings: Co-administration of Letrozole with tamoxifen, other anti-oestrogens or oestrogen-containing therapies should be avoided as these substances may diminish the pharmacological action of letrozole. As the tablets contain lactose, Letrozole is not recommended for patients with rare hereditary problems of galactose intolerance, of severe lactase deficiency or of glucose-galactose malabsorption.

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 Femara are: skeletal events such as osteoporosis and/or bone fractures and cardiovascular events (including cerebrovascular and thromboembolic events).
See prescribing information for full details.

Metabolism of letrozole is partly mediated via CYP2A6 and CYP3A4. Cimetidine, a weak, unspecific inhibitor of CYP450 enzymes, did not affect the plasma concentrations of letrozole. The effect of potent CYP450 inhibitors is unknown.
There is no clinical experience to date on the use of Letrozole in combination with oestrogens or other anticancer agents, other than tamoxifen. Tamoxifen, other anti-oestrogens or oestrogen-containing therapies may diminish the pharmacological action of letrozole. In addition, co-administration of tamoxifen with letrozole has been shown to substantially decrease plasma concentrations of letrozole. Co-administration of letrozole with tamoxifen, other anti-oestrogens or oestrogens should be avoided.
In vitro, letrozole inhibits the cytochrome P450 isoenzymes 2A6 and, moderately, 2C19, but the clinical relevance is unknown. Caution is therefore indicated when giving letrozole concomitantly with medicinal products whose elimination is mainly dependent on these isoenzymes and whose therapeutic index is narrow (e.g. phenytoin, clopidrogel). 

Pregnancy: Based on human experience in which there have been isolated cases of birth defects (labial fusion, ambiguous genitalia), Letrozole may cause congenital malformations when administered during pregnancy. Femara is contraindicated during pregnancy.
Lactation: It is unknown whether letrozole and its metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Letrozole is contraindicated during breast-feeding.
See prescribing information for full details.

Isolated cases of overdose with Letrozole have been reported. No specific treatment for overdose is known; treatment should be symptomatic and supportive.

Storage: Do not store above 30°C. Protect from moisture.