Each film coated tablet contains 2.5 mg of Letrozole.
Excipients/Inactive Ingredients: Colour: Approved colours.
Letrozole is described chemically as 4,4'-(1H-1,2,4-Triazol-1ylmethylene) dibenzonitrile. The molecular formula is C17H11N5 and the molecular weight is 285.31. Letrozole is a white to yellowish crystalline powder, freely soluble in dichloromethane, slightly soluble in alcohol, and practically insoluble in water.
Pharmacotherapeutic group: Antineoplastic Agents
Pharmacology: Pharmacodynamics: Mechanism of Action: Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens. In adult nontumor- and tumor-bearing female animals, letrozole is as effective as ovariectomy in reducing uterine weight, elevating serum Luteinizing hormone (LH), and causing the regression of estrogen-dependent tumors. In contrast to ovariectomy, treatment with letrozole does not lead to an increase in serum (follicle stimulating hormone (FSH). Letrozole selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis.
Pharmacokinetics: Letrozole is rapidly and completely absorbed from the gastrointestinal tract and absorption is not affected by food. It is metabolized slowly to an inactive metabolite whose glucuronide conjugate is excreted renally, representing the major clearance pathway. About 90% of radiolabeled letrozole is recovered in urine. Letrozole's terminal elimination half-life is about 2 days and steady-state plasma concentration after daily 2.5 mg dosing is reached in 2-6 weeks. Plasma concentrations at steady-state are 1.5 to 2 times higher than predicted from the concentrations measured after a single dose, indicating a slight non-linearity in the pharmacokinetics of letrozole upon daily administration of 2.5 mg. These steady-state levels are maintained over extended periods, however, and continuous accumulation of letrozole does not occur. Letrozole is weakly protein bound and has a large volume of distribution (approximately 1.9 L/kg).
Metabolism and Excretion: Metabolism to a pharmacologically-inactive carbinol metabolite (4,4'-methanol bisbenzonitrile) and renal excretion of the glucuronide conjugate of this metabolite is the major pathway of Letrozole clearance. Of the radiolabel recovered in urine, at least 75% was the glucuronide of the carbinol metabolite, about 9% was two unidentified metabolites, and 6% was unchanged letrozole.
In human microsomes with specific CYP isozyme activity, CYP 3A4 metabolized Letrozole to the carbinol metabolite while CYP 2A6 formed both this metabolite and its ketone analog. In human liver microsomes, letrozole strongly inhibited CYP 2A6 and moderately inhibited CYP2C19.
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 hormone 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.
Adult and elderly patients: The recommended dose of Letvex is 2.5 mg once daily. In the adjuvant setting, treatment with Letvex should continue for 5 years or until tumour relapse occurs, whichever comes first. Following standard adjuvant tamoxifen therapy, treatment with Letvex should continue for 5 years or until tumour relapse occurs, whichever comes first. In patients with metastatic disease, treatment with Letvex should continue until tumour progression is evident. Regular monitoring to observe progression during the pre-operative treatment period is recommended. No dose adjustment is required for elderly patients.
Children: Not recommended for use in children.
Patients with hepatic and/or renal impairment: No dosage adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh grade A and B) or renal impairment (creatinine clearance ≥10 mL/min.).
There is no experience of overdosage.
Known hypersensitivity to the active substance or to any of the excipients. Premenopausal, pregnant or lactating women.
Patients with severe hepatic impairment (Child-Pugh grade C).
Pre-operative use of Letrozole is contraindicated if the receptor status is negative or unknown.
Letvex is not recommended for use in children as efficacy and safety in this patient group have not been assessed in clinical studies. There are no efficacy data to support the use of Letvex in men with breast cancer.
Letvex has not been investigated in patients with creatinine clearance <10 mL/min. The potential risk/benefit to such patients should be carefully considered before administration of Letvex.
As Letvex is a potent oestrogen lowering agent, reductions in bone mineral density can be anticipated. During adjuvant treatment with Letvex, women with osteoporosis or at risk of osteoporosis should have their bone mineral density formally assessed by bone densitometry e.g. DEXA scanning at the commencement of treatment. Treatment for osteoporosis should be initiated as appropriate and patients treated with Letvex should be carefully monitored.
It is contraindicated in pregnancy and lactation.
The most common adverse reactions (>20%) were hot flashes, arthralgia; flushing, asthenia, edema, headache, dizziness, hypercholesterolemia, sweating increased, bone pain; and musculoskeletal.
Tamoxifen: Coadministration of letrozole tablets and tamoxifen 20 mg daily resulted in a reduction of letrozole plasma levels of 38% on average. Clinical experience in the second-line breast cancer trials indicates that the therapeutic effect of letrozole therapy is not impaired if letrozole tablet is administered immediately after tamoxifen.
Cimetidine: A pharmacokinetic interaction study with cimetidine showed no clinically significant effect on letrozole pharmacokinetics.
Warfarin: An interaction study with warfarin showed no clinically significant effect of letrozole on warfarin pharmacokinetics.
Store below 30°C. Protect from light and moisture.
Shelf-Life: 2 years from manufacturing date.
L02BG04 - letrozole ; Belongs to the class of enzyme inhibitors. Used in treatment of neoplastic diseases.
FC tab 2.5 mg (light yellow, round, biconvex) x 3 x 10's.