Endofree 2.5

Indications

• Adjuvant Treatment: For postmenopausal women with hormone receptor-positive early breast cancer.
• Extended Adjuvant Therapy: Suitable for postmenopausal women with early breast cancer (with positive or unknown estrogen or progesterone receptor status) who have completed 5 years of adjuvant tamoxifen therapy.
• First-Line Therapy: For postmenopausal women diagnosed with hormone-dependent advanced breast cancer.
• Advanced Breast Cancer Treatment: For women with natural or artificially induced postmenopausal status previously treated with antioestrogens.
• Pre-Operative Therapy: In postmenopausal women with localized hormone receptor-positive breast cancer to facilitate breast-conserving surgery for those initially deemed unsuitable. Follow-up treatment post-surgery should align with standard care protocols. Consult a registered healthcare provider before using this medication.

Pharmacology

Mechanism of Action: Letrozole is a highly selective non-steroidal aromatase inhibitor. It functions by competitively inhibiting the aromatase enzyme, leading to decreased estrogen production in various tissues. This reduction starves estrogen-dependent breast cancer cells of their growth stimulus. In postmenopausal women, estrogens primarily arise from adrenal androgens converted by aromatase into estrone (E1) and estradiol (E2). Letrozole effectively suppresses estrogen biosynthesis in both peripheral and malignant tissues through this targeted inhibition.

In healthy postmenopausal women, doses of 0.1, 0.5, and 2.5 mg of letrozole have been shown to reduce serum estrone and estradiol levels by 75-78% and 78%, respectively, from baseline, achieving maximum suppression within 48-78 hours. In postmenopausal patients with advanced breast cancer, daily doses ranging from 0.1 to 5 mg result in a 78-95% reduction in plasma concentrations of estradiol, estrone, and estrone sulfate. Importantly, letrozole does not significantly affect plasma androgen levels in healthy postmenopausal women, indicating that estrogen biosynthesis inhibition does not lead to an accumulation of androgen precursors.

Pharmacokinetics: Letrozole is rapidly and completely absorbed from the gastrointestinal tract (absolute bioavailability of 99.9%). Although food may slightly slow absorption, it does not affect the total absorption amount, allowing flexibility in administration with or without food. Approximately 60% of letrozole binds to plasma proteins, predominantly albumin (55%). Its metabolic clearance primarily produces an inactive carbinol metabolite, with an average terminal elimination half-life of around 2 days. Steady-state levels are typically reached within 2 to 6 weeks after daily administration of 2.5 mg.

Dosage & Administration

For Adults and the Elderly: The recommended dosage of Letrozole is 2.5 mg once daily. In adjuvant and extended adjuvant settings, treatment should continue for 5 years or until tumor relapse occurs, whichever comes first. For metastatic disease, treatment should persist until evident tumor progression. No dosage adjustments are necessary for elderly patients.

For Patients with Hepatic and/or Renal Impairment: No dosage adjustment is required for those with mild to moderate hepatic or renal impairment (creatinine clearance ≥10 mL/min). Patients with severe hepatic impairment (Child-Pugh score C) should be closely monitored.

For Children: Not applicable. Consult a registered healthcare provider before using this medication.

Interaction

Clinical studies indicate that co-administration of Endofree with cimetidine and warfarin does not lead to significant drug interactions, despite cimetidine being a known inhibitor of cytochrome P450 enzymes that metabolize Endofree in vitro.

Contraindications

Letrozole is contraindicated in individuals with known or suspected hypersensitivity to letrozole or other aromatase inhibitors, during pregnancy and lactation, and in premenopausal women. It is also contraindicated in cases of severe hepatic dysfunction.

Side Effects

Common Side Effects: Hot flashes, elevated cholesterol levels (hypercholesterolemia), fatigue, increased sweating, joint and bone pain (arthralgia), skin rashes, headaches, dizziness, malaise, gastrointestinal issues (nausea, vomiting, indigestion, constipation, diarrhea), changes in appetite, muscle pain, osteoporosis leading to fractures, peripheral edema, depression, weight gain, hair loss, hypertension, abdominal discomfort, dry skin, vaginal bleeding, palpitations, rapid heartbeat, joint stiffness, and chest pain.

Rare Side Effects: Neurological disorders (anxiety, irritability, drowsiness, memory issues), sleep disturbances, carpal tunnel syndrome, sensory impairment, vision problems, skin reactions (itching), vaginal dryness or discharge, urinary tract infections, cough, elevated enzyme levels, jaundice, and increased bilirubin levels.

Pregnancy & Lactation

Studies in pregnant rats indicate that letrozole may cause teratogenic effects and maternal toxicity. Due to the absence of well-controlled studies in pregnant women, its use is not recommended during pregnancy. It is also unknown if letrozole is excreted in human milk, so nursing mothers should avoid its use.

Precautions & Warnings

While no dosage adjustments are needed for breast cancer patients with moderate hepatic dysfunction, caution is advised due to the dependence of Endofree elimination on metabolic clearance. Renal impairment (creatinine clearance: 20 to 50 mL/min) does not necessitate dosage adjustments. Endofree may be removed from the blood through dialysis due to its weak protein binding. Patients should be aware that fatigue and dizziness might impair their ability to operate machinery or drive.

Overdose Effects

There is limited clinical experience regarding overdose. No specific antidote exists for Endofree. Dialysis may be beneficial, and emesis may be induced if the patient is alert. General supportive care and monitoring of vital signs are recommended.

Therapeutic Class

Hormonal Chemotherapy

Storage Conditions

Store below 30°C, protected from light and moisture. Keep out of reach of children.