Letrozol Genthon (Letrozole)

Letrozole is used in endocrine therapy for estrogen‑dependent breast cancer.

• Metastatic breast cancer (postmenopausal): Reduces tumor progression by lowering estrogen levels.
• Early‑stage hormone receptor‑positive breast cancer (postmenopausal) as adjuvant therapy: Decreases risk of disease recurrence after surgery.
• Extended adjuvant therapy after 5 years of tamoxifen (postmenopausal): Provides continued estrogen suppression to further lower recurrence risk.

• Letrozole is a reversible, non‑steroidal inhibitor of the aromatase enzyme (CYP19A1). By binding to the enzyme’s heme group, it blocks the conversion of androstenedione and testosterone to estrone and estradiol, respectively. This results in markedly reduced peripheral estrogen synthesis in postmenopausal women, limiting estrogen‑driven proliferation of hormone‑sensitive breast cancer cells. The inhibition is dose‑dependent and persists for several days after the drug is cleared, allowing once‑daily oral dosing.

Letrozole may cause a range of adverse reactions, which are generally categorized by frequency and severity.

Common Side Effects

• Hot flashes: Sudden feeling of warmth, often with sweating.
• Joint and muscle pain: Arthralgia or myalgia affecting daily activities.
• Fatigue: Persistent tiredness not relieved by rest.
• Nausea or vomiting: Gastrointestinal discomfort that may affect appetite.
• Headache: Persistent or intermittent head pain.
• Insomnia: Difficulty falling or staying asleep.

Serious or Rare Side Effects

• Severe liver injury: Jaundice, elevated enzymes, or hepatic failure.
• Thromboembolic events: Deep vein thrombosis or pulmonary embolism.
• Bone fracture: Increased risk of osteoporosis‑related fractures.

When prescribing Letrozole, several precautions should be observed to ensure patient safety.

• Contraindication in pregnancy: Use is prohibited in pregnant women (Category X).
• Not indicated for premenopausal patients: Efficacy relies on low estrogen baseline.
• Bone health monitoring: Assess bone mineral density regularly due to increased fracture risk.
• Liver function assessment: Perform baseline and periodic liver enzyme tests.
• Drug interactions: Review concomitant estrogen‑containing therapies and CYP2A6 inhibitors.
• Store at ambient temperature: Keep below 25 °C in original packaging, protect from moisture.

Letrozole can interact with several medicines, requiring careful review before co‑administration.

Major Interactions (Avoid)

• Estrogen replacement therapy: Counteracts aromatase inhibition and diminishes therapeutic effect.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): May lower plasma concentrations, reducing efficacy.

Moderate Interactions (Monitor Closely)

• CYP2A6 inhibitors (e.g., fluvoxamine): Can increase letrozole exposure, requiring monitoring.
• Warfarin: Potential alteration of anticoagulant effect; monitor INR.
• Tamoxifen: May interfere with endocrine pathways; assess clinical response.
• Cholesterol‑lowering agents (e.g., statins): May modestly affect metabolism; observe for adverse effects.