Letrozole Accord Healthcare Ireland Limited (Letrozole)

Letrozole is an aromatase inhibitor used in the management of estrogen‑dependent breast cancer.

• Hormone receptor‑positive breast cancer (postmenopausal): Lowers estrogen levels to inhibit tumor growth.
• Adjuvant therapy for early‑stage breast cancer: Reduces risk of disease recurrence after surgery.
• Metastatic breast cancer in postmenopausal women: Controls disease progression by maintaining low estrogen.
• Combination with other endocrine agents: Enhances overall treatment efficacy in hormone‑sensitive disease.
• Neoadjuvant setting before surgery: May shrink tumor size to facilitate breast‑conserving procedures.
• Off‑label investigational use in estrogen‑dependent gynecologic conditions: Under clinical study for potential benefit.

• Letrozole exerts its effect by reversibly binding to the aromatase enzyme (CYP19A1) in peripheral tissues, blocking the conversion of androgens (androstenedione and testosterone) into estrogens (estrone and estradiol). This inhibition markedly reduces circulating estrogen concentrations, depriving estrogen‑dependent tumor cells of a growth stimulus, thereby slowing or halting tumor proliferation. The inhibition is dose‑dependent and selective, with minimal impact on other cytochrome P450 pathways, preserving progesterone synthesis and minimizing interference with non‑target hormonal processes.

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 and sweating.
• Joint and muscle pain: arthralgia and myalgia.
• Fatigue: persistent tiredness.
• Nausea: mild gastrointestinal upset.
• Headache: mild to moderate intensity.
• Dizziness: light‑headed sensation.

Serious or Rare Side Effects

• Severe liver injury: hepatitis or hepatic failure.
• Bone fracture: increased risk of osteoporosis‑related fractures.
• Deep vein thrombosis: formation of blood clots in deep veins.
• Pulmonary embolism: blockage of pulmonary arteries.
• Anaphylaxis: severe allergic reaction requiring emergency care.

When prescribing Letrozole, clinicians should consider several precautionary measures to ensure patient safety.

• Pregnancy: contraindicated (Category X); avoid use in pregnant women.
• Menopausal status: indicated only for postmenopausal patients.
• Bone health: monitor bone mineral density and consider calcium/vitamin D supplementation.
• Liver function: assess hepatic function before initiation and periodically thereafter.
• Drug interactions: review concomitant medications for potential interactions.
• Store at ambient temperature: keep below 25°C in original packaging, protect from moisture.

Letrozole can interact with other medicines, affecting its efficacy or safety.

Major Interactions (Avoid)

• Estrogen‑containing hormone therapy: may counteract Letrozole’s effect.
• Tamoxifen: combined use reduces therapeutic benefit.
• Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine): markedly lower Letrozole plasma levels.
• Ketoconazole: potent CYP3A4 inhibitor that can increase Letrozole levels.

Moderate Interactions (Monitor Closely)

• CYP2C19 inhibitors (e.g., fluconazole, omeprazole): may increase Letrozole exposure.
• Warfarin: potential alteration of INR; monitor coagulation.
• SSRIs (e.g., fluoxetine): may affect estrogen metabolism; observe clinical response.
• Anticonvulsants (e.g., phenytoin): may modestly reduce Letrozole concentrations; monitor efficacy.