Letrozol Accord (Letrozole)

Letrozole is an aromatase inhibitor used in hormone‑dependent breast cancer management.

• Hormone receptor‑positive metastatic breast cancer: reduces tumor progression by markedly lowering estrogen levels.
• Early‑stage hormone receptor‑positive breast cancer (adjuvant setting): decreases the risk of disease recurrence after surgery.
• Postmenopausal estrogen‑dependent breast cancer: provides systemic therapy when tumors rely on estrogen for growth.
• Neoadjuvant therapy for locally advanced breast cancer: shrinks tumor size before definitive surgery.

• Letrozole selectively binds to the aromatase enzyme (CYP19A1) in peripheral tissues, inhibiting the conversion of androstenedione and testosterone to estrone and estradiol. By blocking this final step of estrogen biosynthesis, systemic estrogen concentrations fall markedly, depriving estrogen‑dependent tumor cells of a growth stimulus. The inhibition is competitive and reversible, allowing dose‑dependent control of estrogen levels without affecting other steroid pathways.

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, sweating, and flushing, often occurring at night.
• Joint and muscle pain: arthralgia and myalgia that may limit mobility.
• Fatigue: persistent tiredness affecting daily activities.
• Nausea: mild to moderate upset stomach, sometimes with loss of appetite.
• Headache: occasional mild to moderate headache.

Serious or Rare Side Effects

• Osteoporosis: decreased bone mineral density that can lead to fractures, especially with long‑term use.
• Severe liver dysfunction: marked elevation of transaminases, hepatitis, or hepatic failure.
• Cardiovascular events: thrombosis, myocardial infarction, or stroke in susceptible patients.
• Deep vein thrombosis: clot formation in deep veins, potentially causing swelling and pain.
• Allergic reactions: rash, pruritus, angioedema, or anaphylaxis.

When prescribing Letrozole, clinicians should consider several precautionary measures to ensure safe use.

• Pregnancy contraindication: not to be used in pregnancy; teratogenic risk (Category X).
• Breastfeeding restriction: contraindicated during lactation; may pass into milk.
• Bone health monitoring: assess bone mineral density regularly due to risk of osteoporosis.
• Liver function assessment: evaluate hepatic enzymes before initiation and during therapy.
• Drug interactions: review concomitant medications that affect CYP2A6 or estrogen levels.
• Store at ambient temperature: keep below 25 °C, in original packaging, protected from moisture and light.

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

Major Interactions (Avoid)

• Strong CYP2A6 inducers (e.g., rifampin): may reduce letrozole plasma concentrations.
• Estrogen‑containing hormone therapy: antagonizes therapeutic effect.

Moderate Interactions (Monitor Closely)

• Antifungal agents (e.g., ketoconazole): may increase letrozole levels.
• Anticoagulants (e.g., warfarin): potential alteration of INR.
• Selective serotonin reuptake inhibitors (SSRIs): may affect bone health when combined.
• Tamoxifen: concurrent use may diminish anti‑estrogenic benefit.