Létrozole Biogaran

Uses

• Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.
• Extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy.
• First-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer.
• Treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.

Létrozole Biogaran is also used to associated treatment for these conditions: Advanced Breast Cancer, Anovulatory cycle, Early Breast Cancer, Ovarian Epithelial Cancer, Advanced HR + HER2 - breast cancer, Metastatic HR + HER2 - breast cancer

How Létrozole Biogaran works

Létrozole Biogaran is a non-steroidal type II aromatase inhibitor. It blocks the active site, and therefore the electron transfer chain of CYP19A1. This competitive inhibition prevents the conversion of androgens to estrogen. This action leads to a reduction in uterine weight and elevated leuteinizing hormone. In postmenopausal women, the action of aromatase is responsible for the majority of estrogen production. With reduced availability of estrogen, estrogen-dependant tumors regress. Third generation aromatase inhibitors do not significantly affect cortisol, aldosterone, and thyroxine levels.

Dosage

Létrozole Biogaran dosage

The recommended dose is one 2.5 mg tablet administered once a day, regardless to meals. In patients with advanced disease, treatment with Létrozole Biogaran Tablet should be continued until tumor progression is evident. Treatment should be discontinued at tumor relapse. No dose adjustment is required for elderly patients. Patients treated with Létrozole Biogaran Tablet do not require glucocorticoid or mineralocorticoid replacement therapy.

Side Effects

Létrozole Biogaran is generally well tolerated. The observed adverse reactions are mild or moderate in nature including hot flashes, night sweats, weight increase, nausea, vaginal bleeding & irritation, endometrial proliferation disorders etc.

Toxicity

Overdose data in humans is not readily available, however 1 reported case was not associated with serious adverse reactions. Animal studies do not report serious adverse effects with high dose treatment. Patients experiencing and overdose should be treated with symptomatic and supportive measures.

Oral doses over 2000mg/kg were associated with reduced motor activity, ataxia, dyspnea, and death in mice and rats.

Precaution

Since fatigue and dizziness have been observed with the use of Létrozole Biogaran and somnolence was uncommonly reported, caution is advised when driving or using machinery.

Interaction

A pharmacokinetic interaction study with cimetidine & warfarin showed no clinically significant effect on Létrozole Biogaran pharmacokinetics. In in-vitro experiments, Létrozole Biogaran & diazepam showed no significant inhibition in the metabolism of each other. Coadministration of Létrozole Biogaran and tamoxifen 20 mg daily resulted in a reduction of Létrozole Biogaran plasma levels of 38% on average. Clinical experience in the second-line breast cancer pivotal trials indicates that the therapeutic effect of Létrozole Biogaran therapy is not impaired if Létrozole Biogaran is administered immediately after tamoxifen.

Food Interaction

• Take with or without food. Food slows absorption without decreasing the quantity absorbed.

Létrozole Biogaran Cholesterol interaction

[Moderate] In an adjuvant clinical trial hypercholesterolemia was reported in 52.3% of letrozole patients and 28.6% of tamoxifen patients.

CTC grade 3-4 hypercholesterolemia was reported in 0.4% of letrozole patients and 0.1% of tamoxifen patients.

Also in the adjuvant setting, an increase of >=1.5 X ULN in total cholesterol (generally non-fasting) was observed in patients on monotherapy who had baseline total serum cholesterol within the normal range (i.e.,

Létrozole Biogaran Drug Interaction

Unknown: aspirin, aspirin, calcium / vitamin d, calcium / vitamin d, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, palbociclib, palbociclib, metoprolol, metoprolol, levothyroxine, levothyroxine, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, cetirizine, cetirizine

Létrozole Biogaran Disease Interaction

Major: liver diseaseModerate: cholesterol, osteoporosis

Volume of Distribution

The volume of distribution of letrozole is 1.87L/kg.

Elimination Route

Létrozole Biogaran is 99.9% orally bioavailable. A 2.5mg oral dose reaches a C_max of 104nmol/L with a T_max of 8.10h, and an AUC of 7387nmol*h/L.

Half Life

The terminal elimination half life of letrozole is approximately 42h in healthy volunteers, but longer in breast cancer patients.

Clearance

The average clearance after a single dose of letrozole was 1.52L/h and at steady state was 1.20L/h.

Elimination Route

Létrozole Biogaran is 90% eliminated in the urine. 75% of the dose is recovered as a glucuronide metabolite, 9% is in the form of the ketone and carbinol metabolites, and 6% is recovered in urine as unchanged letrozole.

Pregnancy & Breastfeeding use

Pregnancy Category D. It is not known if Létrozole Biogaran is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Létrozole Biogaran is administered to a nursing woman.

Contraindication

Létrozole Biogaran may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Létrozole Biogaran is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Special Warning

Renal Impairment: No dosage adjustment is required for patients with renal impairment if creatinine clearance is 10 ml/min.

Hepatic Impairment: No dosage adjustment is recommended for patients with mild to moderate hepatic impairment. The dose of Létrozole Biogaran in patients with cirrhosis and severe hepatic dysfunction should be reduced by 50%. The recommended dose for such patients is 2.5 mg administered every other day.

Pediatric Use: The safety and effectiveness in pediatric patients have not been established.

Acute Overdose

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

Storage Condition

Store in a cool and dry place protected from light and moisture.

Innovators Monograph

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