Letrozol Viatris (Letrozole)

• Letrozole is used in the management of hormone‑dependent breast cancer, targeting estrogen‑driven tumor growth.
• Adjuvant treatment of early‑stage hormone receptor‑positive breast cancer: reduces risk of recurrence after surgery.
• Metastatic hormone receptor‑positive breast cancer: slows disease progression and prolongs survival.
• Neoadjuvant therapy before surgery: decreases tumor size to facilitate breast‑conserving procedures.

• Letrozole reversibly binds to the aromatase enzyme, a cytochrome P450 isoform responsible for converting androstenedione and testosterone into estrone and estradiol. By non‑steroidal inhibition of aromatase, it markedly lowers systemic estrogen levels, depriving estrogen‑dependent tumor cells of a growth stimulus. The reduction in circulating estrogen is sustained throughout daily dosing, providing continuous endocrine suppression in postmenopausal patients. This mechanism contributes to tumor control in estrogen‑sensitive cancers.

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

Common Side Effects

• Hot flashes: sudden feeling of warmth, often with sweating.
• Joint and muscle pain: arthralgia or myalgia.
• Fatigue: persistent tiredness.
• Nausea or mild gastrointestinal upset.
• Headache: occasional throbbing pain.

Serious or Rare Side Effects

• Severe liver injury: elevated transaminases or hepatitis.
• Bone fracture: increased risk of osteoporosis‑related fractures.
• Pulmonary embolism: sudden shortness of breath or chest pain.
• Allergic reaction: rash, itching, swelling, or anaphylaxis.
• QT interval prolongation: cardiac rhythm disturbances.

• Before initiating Letrozole therapy, clinicians should consider several precautionary measures to ensure patient safety.
• Assess bone health: evaluate baseline bone mineral density and consider calcium/vitamin D supplementation.
• Monitor liver function: obtain baseline and periodic liver enzyme tests.
• Avoid use in pregnancy: teratogenic risk is unknown; contraindicated in pregnant women.
• Caution in cardiovascular disease: monitor for thromboembolic events.
• Store at room temperature: keep in the original container, protect from moisture and direct sunlight.

Letrozole can interact with other medicines, altering its effectiveness or increasing toxicity.

Major Interactions (Avoid)

• Estrogen replacement therapy: concurrent use reduces Letrozole’s anti‑estrogen effect.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may markedly lower Letrozole plasma concentrations.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may increase Letrozole exposure and risk of adverse events.

Moderate Interactions (Monitor Closely)

• Warfarin: Letrozole may enhance anticoagulant effect, requiring INR monitoring.
• Tamoxifen: combined use can interfere with metabolic activation of tamoxifen.
• CYP2C19 inhibitors (e.g., fluconazole): may affect Letrozole metabolism.