LETROZOLE 25 (FEMARA)Strength: 2,5 mgMolecular Formula: C17HNSMolecular Weight: 285.31 g/molActive Ingredient: LetrozoleCAS number: 11280951-5Dosage Form: TabletRoute: OralMarket Status: PrescriptionCompany: Hilma BiocareDESCRIPTIONLetrozole is a nonsteroidal inhibitor of estrogen synthesis with antineoplastic activity. As athird-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 inmany tissues including those of the premenopausal ovary, liver, and breast, catalyzes thearomatization of androstenedione and testosterone into estrone and estradiol, the final stepin estrogen biosynthesis. Pharmacodynamic effects The elimination of oestrogen-mediatedgrowth stimulation is a prerequisite for tumour response in cases where the growth of tumourtissue depends on the presence of oestrogens and endocrine therapy is used. Inpostmenopausal women, oestrogens are mainly derived from the action of the aromataseenzyme, which converts adrenal androgens – primariy androstenedione and testosterone – tooestrone and oestradiol. The suppression of oestrogen biosynthesis in peripheral tissuesand the cancer tissue itself can therefore be achieved by specifically inhibiting the aromataseenzyme. In healthy postmenopausal women, Single doses of 0.1 mg, 0.5 mg, and 2.5 mgLetrozole suppress serum oestrone and oestradiol by 75%-78% and 78% from baselinerespectively. Maximum suppression is achieved in 48-78 hours. In postmenopausal patientswith advanced breast cancer, daily doses of 0.1 mg to 5 mg suppressed plasmaconcentration of oestradiol, oestrone, and oestrone sulphate by 75-95% from baseline in allpatients treated. With doses of 0.5 mg and higher, many values of oestrone and oestronesulphate were below the limit of detection in the assays, indicating that higher oestrogensuppression is achieved with these doses. Oestrogen suppression was maintainedthroughout treatment in all these patients. No changes were noted in plasmaedoconcentrations of androgens (androstenedione and testosterone)on among healthypostmenopausal women after 0.1 mg, 0.5 mg, and 2.5 mg single doses of Letrozole or inplasma concentrations of androstenedione among postmenopausal patients treated withdaily doses of 0.1 mg to 5 mg, indicating that the blockade of oestrogen biosynthesis doesnot lead to accumulation of androgenic precursors. Plasma levels of LH and FSH are notaffected by Letrozole in patients, nor is thyroid function as evaluated by TSH, T4, and T3uptake tests.INDICATION LETROZOLE 25 (FEMARA)For the extended adjuvant treatment of early breast cancer in postmenopausal women whohave received 5 years of adjuvant Tamoxifen therapy. Also for first-line treatment ofpostmenopausal women with homone receptor positive or hormone receptor unknownlocally advanced or metastatic breast cancer. Also indicated for the treatment of advancedbreast cancer in postmenopausal women with disease progression following antiestrogentherapy.ADMINISTRATIONPosology In patients with advanced or metastatic breast cancer, treatment with Letrozoleshould continue until tumour progression is evident. In the adjuvant and extended adjuvantsetting, 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 yearsfollowed by Tamoxifen 3 years).gonaM In the neoadjuvant setting, treatment with Letrozolecould be continued for 4 to 8 months in order to establish optimal tumour reduction. If theresponse is not adequate, treatment with this product should be discontinued and surgeryscheduled and/or further treatment options discussed with the patient. This product is notrecommended for use in children and adolescents. The safety and efficacy of Letrozole inchildren and adolescents aged up to 17 years have not been established, Limited data areavailable 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-feedingWARNINGS AND PRECAUTIONS FOR USE LETROZOLE 25 (FEMARA)Renal impairment No dosage adjustment of Letrozole is required for patients with renalinsufficiency with creatinine clearance> 10 ml/min, Insufficient data are available in cases ofrenal insufficiency with creatinine clearance lower than 10 ml/min. Hepatic impairment Nodose adjustment of this product is required for patients with mild to moderate hepaticinsufficiency (Child- Pugh A or B). Insufficient data are available for patients with severehepatic impairment. Patients with severe hepatic impairment (Child-Pugh C) require closesupervision. Menopausal status In patients whose menopausal status is unclear, luteinisinghormone (LH), follicle-stimulating hormone (FSH) and/or oestradiol levels should bemeasured before initiating treatment with Letrozole. Only women of postmenopausalendocrine status should receive this product. Bone effects Letrozole is a potentoestrogen-lowering agent. Women with a history of osteoporosis and/or fractures, or who areat increased risk of osteoporosis, should have their bone mineral density formally assessedprior to the commencement of adjuvant and extended adjuvant treatment and monitoredduring and following treatment with Letrozole. Treatment or prophylaxis for osteoporosisshould be initiated as appropriate and carefully monitored. In the adjuvant setting asequential treatment schedule (Letrozole 2 years followed by Tamoxifen 3 years) could alsobe considered depending on the patient’s safety profile. Other warnings Co-administration ofThis product with Tamoxifen, other anti-oestrogens or oestrogen-containing therapies should beavoided as these substances may diminish the pharmacological action of Letrozole, ifoverwise is not directed by physician. As the tablets contain lactose, Letrozole is notrecommended for patients with rare hereditary problems of galactose intolerance, of severelactase deficiency or of glucose-galactose malabsorption. Effects on ability to drive and usemachines Letrozole has minor influence on the ability to drive and use machines. Sincefatigue and dizziness have been observed with the use of Letrozole and somnolence hasbeen reported uncommonly, caution is advised when driving or using machines.ADVERSE REACTIONSCommonly reported side effects of letrozole include: bone fracture, arthralgia, edema,dizziness, fatigue, hypercholesterolemia, osteoporosis, and flushing. Other side effectsinclude: 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. Possiblecardiological adverse events for Letrozole and Tamoxifen, respectively let median treatmentduration of 60 months plus 30 days): angina requiring surgery (in 1.0% cases); cardiacfailure (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 ofthis product. The effect of potent CYP450 inhibitors is unknown. There is no clinical experienceto date on the use of Letrozole in combination with oestrogens or other anticancer agents,other than Tamoxifen. Tamoxifen, other anti-oestrogens or oestrogen-containing therapiesmay diminish the pharmacological action of Letrozole. In addition, co-administration ofTamoxifen with Letrozole has been shown to substantially decrease plasma concentrationsof Letrozole. Co- administration of Letrozole with Tamoxifen, other anti-oestrogens oroestrogens should be avoided, unless otherwise specified by the doctor. In vitro, Letrozoleinhibits the cytochrome P450 isoenzymes 2A6 and, moderately, 2C19, but the clinicalrelevance is unknown.DOSAGEThe 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 ofthis product is 2 days.STORAGEStore in a cool dry place between 15-25°C. Protect from lightMore you can find on our website: hilmabioshop.com/shop
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