Letrozole Accord Healthcare (Letrozole)

Letrozole acts on estrogen‑dependent breast cancer pathways, providing therapeutic benefit in hormone‑sensitive disease.

• Estrogen receptor‑positive breast cancer in postmenopausal women: reduces estrogen production to inhibit tumor growth.
• Adjuvant therapy for early‑stage hormone‑receptor‑positive breast cancer: lowers risk of disease recurrence after surgery.
• Metastatic hormone‑receptor‑positive breast cancer: provides disease control by sustained estrogen suppression.

• Letrozole selectively inhibits the aromatase enzyme (CYP19A1), which converts androstenedione and testosterone into estrone and estradiol. By blocking this conversion, systemic estrogen levels fall markedly, depriving estrogen‑dependent tumor cells of a growth stimulus. The inhibition is competitive and reversible, leading to sustained reduction of circulating estrogen while sparing other steroid pathways. The drug binds to the heme group of aromatase, preventing substrate access and thereby decreasing peripheral estrogen synthesis in postmenopausal patients.

Letrozole may cause a range of adverse reactions, varying from mild to serious.

Common Side Effects

• Hot flashes: sudden feeling of warmth and sweating.
• Joint and muscle pain: aching in joints or muscles.
• Fatigue: persistent tiredness.
• Nausea: mild stomach upset.
• Headache: pressure or throbbing pain.

Serious or Rare Side Effects

• Severe liver injury: jaundice, elevated enzymes, hepatic failure.
• Bone fractures: increased risk of osteoporosis‑related fractures.
• Pulmonary embolism: sudden shortness of breath, chest pain.

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

• Bone health monitoring: assess baseline bone mineral density and consider calcium/vitamin D supplementation.
• Liver function assessment: perform baseline hepatic enzymes and monitor periodically.
• Cardiovascular risk evaluation: review history of thromboembolic events and manage risk factors.
• Avoid use in premenopausal women: drug is ineffective and may cause ovarian stimulation.
• Review concomitant medications: check for interactions that may alter letrozole exposure.
• Store at room temperature: keep in original container, protect from moisture and direct sunlight.

Letrozole’s metabolism and pharmacodynamics can be affected by several co‑administered medicines.

Major Interactions (Avoid)

• Estrogen‑containing hormone therapy: antagonizes letrozole’s estrogen‑lowering effect.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): markedly reduce plasma concentrations.
• Tamoxifen: concurrent use may diminish therapeutic benefit and increase toxicity.

Moderate Interactions (Monitor Closely)

• Warfarin: letrozole may enhance anticoagulant effect, requiring INR monitoring.
• Selective serotonin reuptake inhibitors (e.g., fluoxetine): may modestly increase letrozole levels.
• Statins metabolized by CYP3A4 (e.g., simvastatin): monitor for possible increased exposure.