Letrozole Tablets

Approved Indications & Clinical Uses of Letrozole

• Adjuvant Treatment: Standard first-line adjuvant therapy for postmenopausal women with hormone receptor-positive (HR+) early breast cancer.
• Extended Adjuvant Treatment: Indicated for extended adjuvant treatment in postmenopausal women with early breast cancer who have completed approximately 5 years of prior adjuvant tamoxifen therapy.
• Advanced / Metastatic Breast Cancer: First-line treatment for postmenopausal women with advanced or metastatic HR+ or hormone receptor-unknown breast cancer, as well as second-line treatment following anti-estrogen progression.
• Ovulation Induction (Off-Label): Widely utilized in reproductive medicine as a first-line ovulation induction agent for anovulatory infertility in women with Polycystic Ovary Syndrome (PCOS).

Mechanism of Action (How Letrozole Works)

• Aromatase Enzyme Inhibition: Competitively binds to the heme group of the cytochrome P450 unit of the aromatase enzyme (CYP19A1).
• Estrogen Suppression: Inhibits the enzymatic conversion of androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) in peripheral adipose and tumor tissues.
• >95% Circulating Estrogen Depletion: Suppresses serum estradiol, estrone, and estrone sulfate by over 95% to 98% without affecting corticosteroid or aldosterone synthesis.
• Tumor Deprivation: Eliminates estrogen-driven proliferative signaling, halting the growth and metastasis of hormone-sensitive breast neoplasms.

Side Effects of Letrozole Tablets

• Hot flashes, flushing, and nocturnal sweating (night sweats)
• Aromatase inhibitor-associated musculoskeletal syndrome (AIMSS): Arthralgia, joint stiffness, and bone/muscle pain
• Bone mineral density reduction (osteopenia and accelerated osteoporosis)
• Generalized fatigue, asthenia, and malaise
• Headache, dizziness, and sleep disturbances (insomnia)
• Vaginal dryness, irritation, and dyspareunia
• Hypercholesterolemia and elevated serum triglycerides
• Mild nausea, dyspepsia, and constipation

• Increased incidence of low-trauma bone fractures due to bone mineral demineralization
• Cardiovascular and cerebrovascular ischemic events (angina, myocardial infarction, stroke)
• Venous thromboembolic complications (DVT, pulmonary embolism)
• Hepatotoxicity (elevated serum transaminases, bilirubin, or hepatitis)
• Unusual vaginal bleeding or endometrial changes requiring gynecologic evaluation

Clinical Precautions & Guidelines

• Menopausal Status Verification: Letrozole is indicated strictly in women with confirmed postmenopausal status. In premenopausal women with functioning ovaries, aromatase inhibition triggers compensatory gonadotropin hypersecretion and ovarian hyperstimulation; use in premenopausal women requires concomitant ovarian suppression (LHRH agonist).
• Bone Health: Baseline Dual-Energy X-ray Absorptiometry (DEXA) bone density scanning is recommended prior to initiating therapy, followed by regular scans and prophylactic calcium/vitamin D supplementation.
• Hepatic & Renal Caution: Use with close monitoring in patients with severe hepatic impairment (Child-Pugh C) or severe renal dysfunction (CrCl <10 mL/min).
• Lipid Monitoring: Monitor fasting lipid panels, as Letrozole can elevate LDL cholesterol.

Warnings & Contraindications

• Pregnancy & Teratogenicity: Contraindicated in pregnancy. Letrozole causes embryofetal toxicity, congenital malformations, and fetal death.
• Breastfeeding: Avoid breastfeeding during treatment and for at least 3 weeks after the last dose.
• Premenopausal Monotherapy: Contraindicated as monotherapy in premenopausal women.
• Drug Allergy: Contraindicated in patients with known hypersensitivity to Letrozole or any formulation excipients.

Drug Interactions

• Tamoxifen: Concomitant use with tamoxifen reduces plasma concentrations of letrozole by ~38% without providing clinical benefit; simultaneous administration must be avoided.
• Estrogen-Containing Therapies: Oral contraceptives, hormone replacement therapies (HRT), and vaginal estrogen creams counteract letrozole's anti-estrogenic action and are contraindicated.
• Supplements & Phytoestrogens: Over-the-counter supplements containing soy isoflavones, red clover, and DHEA (dehydroepiandrosterone) can diminish therapeutic efficacy.

Parameters to Monitor

• Bone mineral density (DEXA scan at baseline and every 1 to 2 years)
• Serum lipid profile (total cholesterol, HDL, LDL, triglycerides)
• Hepatic function tests (ALT, AST, alkaline phosphatase, bilirubin)
• Cardiovascular assessment and blood pressure monitoring
• Gynecologic evaluation in the event of persistent vaginal bleeding

Storage