Zoleta 2.5 mg

Description

Indications Letrozole is used for the following therapeutic purposes:

• Adjuvant treatment: Prescribed for postmenopausal women with hormone receptor-positive early breast cancer.
• Extended adjuvant therapy: Recommended for postmenopausal women with early breast cancer (with positive or unknown estrogen or progesterone receptor status) who have completed five years of adjuvant tamoxifen therapy.
• First-line therapy: Used in postmenopausal women with hormone-dependent advanced breast cancer.
• Advanced breast cancer treatment: Administered to women with naturally occurring or medically induced postmenopausal status who have previously been treated with anti-estrogen therapy.
• Pre-operative therapy: Given to postmenopausal women with localized hormone receptor-positive breast cancer to facilitate breast-conserving surgery in cases where this option was initially not viable. Subsequent treatment after surgery should align with standard care protocols.

(Take medication as prescribed by a registered physician.)

Pharmacology Mechanism of Action: Letrozole is a highly potent and selective nonsteroidal aromatase inhibitor. It works by competitively binding to the heme group of the cytochrome P450 enzyme, inhibiting aromatase and thereby reducing estrogen biosynthesis in all tissues. This action helps to deprive estrogen-dependent breast cancer cells of their primary growth stimulus.

In postmenopausal women, estrogen is mainly produced by the aromatization of adrenal androgens such as androstenedione and testosterone into estrone (E1) and estradiol (E2). By selectively inhibiting aromatase, letrozole reduces estrogen production in both peripheral and malignant tissues.

Clinical studies indicate that single doses of 0.1, 0.5, and 2.5 mg of letrozole suppress serum estrone and estradiol levels by approximately 75–78% and 78%, respectively, from baseline. Maximum suppression occurs within 48–78 hours. In patients with advanced breast cancer, daily doses between 0.1 mg and 5 mg decrease estradiol, estrone, and estrone sulfate levels by 78–95%. Letrozole does not significantly affect plasma androgen concentrations, suggesting that estrogen suppression does not lead to the accumulation of androgenic precursors. No impairment of adrenal steroidogenesis has been observed.

Pharmacokinetics:

• Absorption: Rapid and complete, with an absolute bioavailability of 99.9%. Food slightly reduces the absorption rate but does not affect the overall extent of absorption.
• Protein Binding: Approximately 60%, primarily to albumin (55%). The concentration in erythrocytes is about 80% of that in plasma.
• Metabolism and Elimination: Primarily metabolized into an inactive carbinol derivative via the cytochrome P450 isoenzymes 3A4 and 2A6. The apparent terminal half-life in plasma is around two days. Steady-state concentrations are achieved within two to six weeks of daily 2.5 mg dosing.

Dosage & Administration

• Adults and Elderly Patients: The standard dose is 2.5 mg once daily.
  • Adjuvant and Extended Adjuvant Therapy: Recommended for five years or until tumor relapse, whichever occurs first.
  • Metastatic Breast Cancer: Continue treatment until tumor progression is evident.
• Patients with Hepatic or Renal Impairment: No dosage adjustments are required for patients 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.
• Children: Not applicable.

(Take medication as prescribed by a registered physician.)

Drug Interactions Clinical studies indicate that co-administration of letrozole with cimetidine or warfarin does not result in clinically significant interactions, despite cimetidine being a known inhibitor of one of the cytochrome P450 enzymes responsible for letrozole metabolism.

Contraindications Letrozole should not be used in patients with:

• Known or suspected hypersensitivity to letrozole or other aromatase inhibitors.
• Pregnancy or lactation.
• Premenopausal status.
• Severe hepatic dysfunction.

Side Effects Common side effects include:

• Hot flashes, increased cholesterol levels (hypercholesterolemia), fatigue, excessive sweating.
• Joint and bone pain (arthralgia), rash, headache, dizziness, general malaise.
• Gastrointestinal issues such as nausea, vomiting, indigestion, constipation, and diarrhea.
• Appetite fluctuations, muscle pain, osteoporosis, swelling (edema), depression, weight gain, hair loss.
• Hypertension, abdominal pain, dry skin, vaginal bleeding, palpitations, rapid heart rate, arthritis, chest pain.

Rare side effects include:

• Nervous system disorders: Anxiety, irritability, drowsiness, memory impairment, insomnia.
• Carpal tunnel syndrome, impaired sensation.
• Eye issues: Blurred vision, eye irritation.
• Skin reactions: Itching (urticaria).
• Vaginal dryness or discharge, mucous membrane dryness, weight loss.
• Urinary tract infections, frequent urination, cough.
• Elevated liver enzymes, jaundice, increased bilirubin levels.

Pregnancy & Lactation Animal studies indicate that letrozole is teratogenic and can cause maternal toxicity at low doses. Embryotoxicity and fetal malformations were observed in preclinical studies. Due to the lack of adequate studies in pregnant women, letrozole is contraindicated during pregnancy and should not be administered to breastfeeding mothers, as its presence in human milk is unknown.

Precautions & Warnings

• Hepatic Dysfunction: Moderate impairment does not require dosage adjustments, but caution is advised since letrozole is metabolized hepatically.
• Renal Impairment: Patients with mild to moderate renal impairment (creatinine clearance 20–50 mL/min) do not require dose adjustments. Letrozole may be removed via dialysis if necessary.
• Cognitive and Physical Effects: Letrozole may cause dizziness and fatigue, which could impair the ability to drive or operate machinery.

Overdose Effects There is no documented clinical experience with letrozole overdose. There is no specific antidote. Since letrozole is not highly protein-bound, dialysis may be beneficial. Supportive care and frequent monitoring of vital signs are recommended.

Therapeutic Class Hormonal Chemotherapy

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