LETROZOLE 25 (FEMARA) (2,5 MG/TAB. – 30 TABS) – Hilma Biocare

LETROZOLE 25 (FEMARA) Strength: 2,5 mg Molecular Formula: C17HNS Molecular Weight: 285.31 g/mol Active Ingredient: Letrozole CAS number: 11280951-5 Dosage Form: Tablet Route: Oral Market Status: Prescription Company: Hilma Biocare DESCRIPTION Letrozole is a nonsteroidal inhibitor of estrogen synthesis with antineoplastic activity. As a third-generation aromatase inhibitor, this product selectively and reversibly inhibits aromatase, which may result in growth inhibition of estrogen- dependent breast cancer cells. Aromatase, a cytochrome P-450 enzyme localized to the endoplasmic reticulum of the cell and found in many tissues including those of the premenopausal ovary, liver, and breast, catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol, the final step in estrogen biosynthesis. Pharmacodynamic effects The elimination of oestrogen-mediated growth stimulation is a prerequisite for tumour response in cases where the growth of tumour tissue depends on the presence of oestrogens and endocrine therapy is used. In postmenopausal women, oestrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens – primariy androstenedione and testosterone – to oestrone and oestradiol. The suppression of oestrogen biosynthesis in peripheral tissues and the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme. In healthy postmenopausal women, Single doses of 0.1 mg, 0.5 mg, and 2.5 mg Letrozole suppress serum oestrone and oestradiol by 75%-78% and 78% from baseline respectively. Maximum suppression is achieved in 48-78 hours. In postmenopausal patients with advanced breast cancer, daily doses of 0.1 mg to 5 mg suppressed plasma concentration of oestradiol, oestrone, and oestrone sulphate by 75-95% from baseline in all patients treated. With doses of 0.5 mg and higher, many values of oestrone and oestrone sulphate were below the limit of detection in the assays, indicating that higher oestrogen suppression is achieved with these doses. Oestrogen suppression was maintained throughout treatment in all these patients. No changes were noted in plasmaedo concentrations of androgens (androstenedione and testosterone)on among healthy postmenopausal women after 0.1 mg, 0.5 mg, and 2.5 mg single doses of Letrozole or in plasma concentrations of androstenedione among postmenopausal patients treated with daily doses of 0.1 mg to 5 mg, indicating that the blockade of oestrogen biosynthesis does not lead to accumulation of androgenic precursors. Plasma levels of LH and FSH are not affected by Letrozole in patients, nor is thyroid function as evaluated by TSH, T4, and T3 uptake tests. INDICATION LETROZOLE 25 (FEMARA) For the extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant Tamoxifen therapy. Also for first-line treatment of postmenopausal women with homone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer. Also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy. ADMINISTRATION Posology 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. In the adjuvant setting a sequential treatment schedule (Letrozole 2 years followed by Tamoxifen 3 years).gonaM In the neoadjuvant setting, treatment with Letrozole could be continued for 4 to 8 months in order to establish optimal tumour reduction. If the response is not adequate, treatment with this product should be discontinued and surgery scheduled and/or further treatment options discussed with the patient. This product 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. CONTRAINDICATIONS FOR LETROZOLE 25 (FEMARA) • Hypersensitivity to the active e substance or to any of the excipients • Premenopausal endocrine status • Pregnancy Breast-feeding WARNINGS AND PRECAUTIONS FOR USE LETROZOLE 25 (FEMARA) 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 this product 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. 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. Only women of postmenopausal endocrine status should receive this product. 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. In the adjuvant setting a sequential treatment schedule (Letrozole 2 years followed by Tamoxifen 3 years) could also be considered depending on the patient’s safety profile. Other warnings Co-administration of This product with Tamoxifen, other anti-oestrogens or oestrogen-containing therapies should be avoided as these substances may diminish the pharmacological action of Letrozole, if overwise is not directed by physician. 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. Effects on ability to drive and use machines Letrozole has minor influence on the ability to drive and use machines. Since fatigue and dizziness have been observed with the use of Letrozole and somnolence has been reported uncommonly, caution is advised when driving or using machines. ADVERSE REACTIONS Commonly reported side effects of letrozole include: bone fracture, arthralgia, edema, dizziness, fatigue, hypercholesterolemia, osteoporosis, and flushing. Other side effects include: myalgia. Less common side effects: bone fracture, breast pain, chest pain, chills, fever, or flu-like symptoms, mental depression, swelling of the feet or lower legs. Possible cardiological adverse events for Letrozole and Tamoxifen, respectively let median treatment duration of 60 months plus 30 days): angina requiring surgery (in 1.0% cases); cardiac failure (1.1% ); hypertension (5.6% %); cerebrovascular accident/transient ischaemic attack (2.1%). Check with your doctor if any side effects occur while taking Letrozole. DRUG INTERACTION LETROZOLE 25 (FEMARA) Metabolism of Letrozole is partly mediated via CYP2A6 and CYP3A4. Cimetidine, a weak, non specific inhibitor of CYP450 enzymes, did not affect the plasma concentrations of this product. 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, unless otherwise specified by the doctor. In vitro, Letrozole inhibits the cytochrome P450 isoenzymes 2A6 and, moderately, 2C19, but the clinical relevance is unknown. DOSAGE The recommended dose of Letrozole tablets is one 2.5 mg tablet administered once a day, without regard to meals. No dose adjustment is required for elderly patients. Half life of this product is 2 days. STORAGE Store in a cool dry place between 15-25°C. Protect from light More you can find on our website: hilmabioshop.com/shop