Lenor

Approved Indications:

• Early Breast Cancer (Adjuvant Treatment):
  Indicated for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.
• Extended Adjuvant Treatment:
  Indicated for extended adjuvant treatment of early breast cancer in postmenopausal women who have completed 5 years of adjuvant tamoxifen therapy.
• Advanced/Metastatic Breast Cancer:
  Indicated as first-line treatment in postmenopausal women with hormone receptor-positive or unknown receptor status locally advanced or metastatic breast cancer.
  Also indicated for advanced breast cancer in postmenopausal women whose disease has progressed following antiestrogen therapy.

Clinically Accepted Off-Label Uses:

• Ovulation Induction in Anovulatory Infertility (e.g., PCOS):
  Used for inducing ovulation in women with polycystic ovary syndrome (PCOS) or unexplained infertility.
• Endometriosis-Associated Infertility:
  Sometimes used in specific fertility treatment protocols to suppress estrogen production and improve outcomes.

Route of Administration: Oral

Adults (Postmenopausal Women):

• Early Breast Cancer (Adjuvant or Extended Adjuvant):
  2.5 mg orally once daily, with or without food, for 5 years or until recurrence.
• Advanced/Metastatic Breast Cancer:
  2.5 mg orally once daily, continued until disease progression or unacceptable toxicity.

Ovulation Induction (Off-label Use):

• 2.5–7.5 mg orally once daily for 5 days, typically starting on Day 3 or Day 5 of the menstrual cycle.

Elderly:
No dose adjustment required.

Renal Impairment:

• Mild to moderate: No adjustment needed.
• Severe renal impairment (CrCl <10 mL/min): Use with caution; limited data available.

Hepatic Impairment:

• Mild to moderate: No dose adjustment needed.
• Severe: Use with caution due to potential increased exposure.

Pediatric Use:
Not recommended. Safety and efficacy not established.

Letrozole is a non-steroidal aromatase inhibitor that selectively blocks the aromatase enzyme, which catalyzes the conversion of androgens (androstenedione and testosterone) into estrogens (estrone and estradiol) in peripheral tissues. In postmenopausal women, this is the primary source of circulating estrogens. By inhibiting estrogen synthesis, Letrozole reduces estrogen levels, thereby depriving hormone receptor-positive breast cancer cells of the estrogen stimulation needed for growth. In ovulation induction, the reduction in estrogen relieves the negative feedback inhibition on the hypothalamic-pituitary axis, leading to increased gonadotropin (FSH) release and stimulation of follicular development.

• Absorption: Rapid and nearly complete; peak plasma concentration in ~1 hour.
• Bioavailability: ~99% (not affected by food).
• Distribution: Volume of distribution ~1.87 L/kg; ~60% plasma protein bound.
• Metabolism: Extensively metabolized in the liver by CYP3A4 and CYP2A6 into an inactive carbinol metabolite.
• Half-Life: ~2 days (range 2–4 days).
• Steady-State: Achieved within 2–6 weeks of daily dosing.
• Excretion: ~90% excreted in urine (mainly as metabolites); ~6% as unchanged drug.

• Pregnancy:
  Contraindicated (FDA Pregnancy Category X). Letrozole may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should use effective contraception during treatment and for at least 3 weeks after the last dose.
• Lactation:
  Unknown whether letrozole is excreted in human milk. Due to potential serious adverse effects on the infant, breastfeeding is not recommended during treatment and for at least 3 weeks after the last dose.

• Primary Class: Antineoplastic agent
• Subclass: Aromatase Inhibitor (Non-steroidal, Type I)

• Known hypersensitivity to Letrozole or any component of the formulation
• Premenopausal women (for cancer treatment)
• Pregnancy
• Breastfeeding

• Bone Mineral Density Loss:
  Long-term estrogen suppression may lead to decreased bone mineral density and increased fracture risk. Monitor BMD periodically.
• Hypercholesterolemia:
  May increase serum cholesterol; monitor lipid profile during treatment.
• Hepatic Impairment:
  Use with caution in severe hepatic dysfunction; plasma concentrations may increase.
• Cardiovascular Events:
  Use with caution in patients with preexisting cardiovascular conditions; small increase in ischemic events observed.
• Ovulation Induction Use:
  Letrozole should be used for ovulation induction only under expert supervision. Teratogenic risk exists if pregnancy occurs during treatment.

Common (≥10%):

• Musculoskeletal: Arthralgia, back pain, osteoporosis
• General: Hot flushes, fatigue
• Neurological: Headache, dizziness
• Gastrointestinal: Nausea, constipation, abdominal discomfort
• Metabolic: Increased cholesterol

Uncommon (1–10%):

• Vaginal bleeding or dryness
• Edema, hypertension
• Depression, anxiety
• Sleep disturbances

Serious or Rare:

• Bone fractures
• Thromboembolic events
• Hepatotoxicity
• Severe allergic reactions

• Tamoxifen:
  May reduce plasma concentrations of Letrozole; avoid concurrent use.
• CYP450 Interactions:
  Letrozole is metabolized by CYP3A4 and CYP2A6; caution with strong inducers or inhibitors, though clinically significant interactions are rare.
• Estrogens:
  Antagonize the pharmacologic action of Letrozole; concurrent use should be avoided.
• Alcohol:
  No known direct interaction, but may increase the risk of liver and bone complications; use cautiously.

• NCCN & ASCO Guidelines:
  Letrozole is a recommended option for first-line and extended adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer.
• Fertility Guidelines:
  Letrozole has gained preference over clomiphene citrate in some infertility protocols due to improved ovulation and lower risk of multiple gestations.
• Safety Monitoring:
  Emphasis on periodic bone mineral density and lipid profile assessments during prolonged use.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity: Protect from moisture
• Light: Store in original packaging to avoid light exposure
• Handling: No special handling required
• Reconstitution: Not applicable