Letrozole Hikma Farmacêutica (Portugal) (Letrozole)

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

• Hormone receptor‑positive breast cancer (postmenopausal): reduces estrogen production to inhibit tumor growth.
• Adjuvant treatment of early‑stage breast cancer: lowers risk of disease recurrence after surgery.
• Metastatic breast cancer (postmenopausal): provides systemic endocrine control of advanced disease.

• Letrozole selectively and non‑competitively inhibits the aromatase enzyme, a cytochrome P450 isoform responsible for converting adrenal and peripheral androgen precursors into estrogens. By blocking this final step in estrogen biosynthesis, systemic estradiol levels fall markedly, depriving estrogen‑dependent tumor cells of a growth stimulus.

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

Common Side Effects

• Hot flashes
• Joint and muscle pain
• Fatigue
• Nausea
• Headache
• Dizziness

Serious or Rare Side Effects

• Osteoporosis or bone fractures
• Elevated liver enzymes or hepatitis
• Severe allergic reactions (anaphylaxis, skin rash)
• Cardiovascular events (thromboembolism, QT prolongation)

When prescribing Letrozole, clinicians should consider several safety measures and monitoring requirements.

• Bone health monitoring: assess baseline bone mineral density and consider calcium/vitamin D supplementation.
• Liver function: evaluate hepatic enzymes before initiation and periodically during therapy.
• Cardiovascular risk: review patient history of thromboembolic disease or QT prolongation.
• Pregnancy avoidance: contraindicated in pregnant women; ensure effective contraception in women of childbearing potential.
• Drug interactions: review concomitant medications that affect CYP3A4 metabolism.
• Store at ambient temperature: keep in original packaging, protect from moisture and direct sunlight.

Letrozole interacts with several medicines that can alter its plasma concentration or therapeutic effect.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may markedly reduce letrozole levels.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may increase letrozole exposure and toxicity.
• Estrogen‑containing hormone therapy: antagonizes letrozole’s estrogen‑lowering action.

Moderate Interactions (Monitor Closely)

• Tamoxifen: combined use may affect endocrine balance; monitor clinical response.
• Warfarin: letrozole may enhance anticoagulant effect; check INR regularly.
• SSRIs (e.g., fluoxetine): potential for modest pharmacokinetic interaction; observe for side effects.
• Cholesterol‑lowering agents (e.g., statins): monitor for hepatic effects.