Letrozol Devatis (Letrozole)

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

• Postmenopausal estrogen receptor‑positive breast cancer: reduces risk of disease recurrence as part of adjuvant therapy.
• Metastatic hormone‑sensitive breast cancer in postmenopausal women: slows disease progression and improves survival.
• Neoadjuvant treatment for estrogen‑driven tumors: facilitates tumor shrinkage before surgery.

• Letrozole selectively binds to the aromatase enzyme (CYP19A1) in peripheral tissues, inhibiting the conversion of androstenedione and testosterone to estrone and estradiol. By lowering circulating estrogen levels, it deprives estrogen receptor‑positive breast cancer cells of a growth stimulus, thereby suppressing tumor proliferation and inducing apoptosis. The inhibition is reversible and dose‑dependent, with minimal impact on cortisol or aldosterone synthesis, allowing selective estrogen suppression without major adrenal effects.

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

Common Side Effects

• Hot flashes: sudden warmth and sweating.
• Joint and muscle pain: arthralgia or myalgia.
• Fatigue: persistent tiredness.
• Nausea: mild gastrointestinal upset.

Serious or Rare Side Effects

• Severe liver injury: marked elevation of liver enzymes or hepatitis.
• Bone fractures: increased risk of osteoporosis‑related fractures.
• Pulmonary embolism: blood clot formation in the lungs.

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

• Pregnancy contraindication: avoid use in pregnant women; drug is teratogenic (Category X).
• Menopause status: confirm postmenopausal status before initiating therapy.
• Bone health monitoring: assess bone mineral density and consider calcium/vitamin D supplementation.
• Liver function: monitor hepatic enzymes regularly during treatment.
• Drug interactions: review concomitant medications for CYP2C19 or CYP3A4 inhibitors or inducers.
• Store at below 25°C: keep in original packaging, protect from moisture and light.

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

Major Interactions (Avoid)

• Strong CYP2C19 inhibitors (e.g., fluconazole, voriconazole): may increase letrozole plasma levels.
• Potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may raise exposure and risk of toxicity.
• Estrogen‑containing hormone therapy: antagonizes therapeutic effect.

Moderate Interactions (Monitor Closely)

• CYP2C19 inducers (e.g., rifampin, carbamazepine): may reduce letrozole effectiveness.
• Warfarin: may require INR monitoring due to potential alteration of anticoagulant effect.
• Selective serotonin reuptake inhibitors (e.g., fluoxetine): may modestly affect metabolism.