Letrozole Teva (Letrozole)

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

• Hormone receptor‑positive early‑stage breast cancer: administered after surgery to lower the chance of cancer returning.
• Hormone receptor‑positive metastatic breast cancer: used to delay tumor growth and extend survival in postmenopausal patients.
• Hormone receptor‑positive breast cancer in postmenopausal women: provides endocrine suppression as part of primary or combined therapy.
• Locally advanced breast cancer (neoadjuvant setting): given before surgery to shrink tumors and improve operability.

• Letrozole selectively and reversibly inhibits the aromatase enzyme (CYP19A1), which converts adrenal and ovarian androgens into estrogens. By blocking this peripheral conversion, systemic estrogen concentrations fall markedly, depriving estrogen‑dependent tumor cells of growth stimulus. The inhibition is dose‑dependent and persists while the drug is present in plasma, leading to sustained estrogen suppression in postmenopausal patients. This mechanism underlies its efficacy in both adjuvant and metastatic treatment settings.

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

Common Side Effects

• Hot flashes: transient episodes of increased skin temperature and sweating.
• Joint and muscle pain: arthralgia or myalgia affecting daily activities.
• Fatigue: persistent tiredness not relieved by rest.
• Nausea: mild to moderate upset stomach.
• Headache: occasional throbbing or pressure sensation.
• Insomnia: difficulty initiating or maintaining sleep.

Serious or Rare Side Effects

• Osteoporosis or bone fracture: decreased bone mineral density leading to fractures.
• Severe liver injury: marked elevation of hepatic enzymes or hepatitis.
• Venous thromboembolism: deep vein thrombosis or pulmonary embolism.
• Cardiovascular events: myocardial infarction or stroke.
• Allergic reactions: rash, angioedema, or anaphylaxis.

Before initiating Letrozole therapy, clinicians should evaluate patient history and monitor specific parameters to minimize risks.

• Assess bone health: perform baseline densitometry and consider calcium/vitamin D supplementation.
• Monitor liver function: check hepatic enzymes periodically during treatment.
• Evaluate cardiovascular risk: screen for hypertension, hyperlipidemia, and prior thrombotic events.
• Review concomitant medications: avoid drugs that may increase estrogen levels or affect metabolism.
• Counsel on pregnancy avoidance: contraindicated in pregnancy; ensure effective contraception.
• Store at ambient temperature: keep tablets below 25 °C in the original container, protected from moisture and light.

Letrozole can interact with other medicines, altering its effectiveness or increasing toxicity.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may reduce letrozole plasma concentrations.
• Estrogen‑containing therapies (e.g., hormone replacement therapy): counteract aromatase inhibition.
• Tamoxifen: combined use may increase risk of adverse hepatic effects.

Moderate Interactions (Monitor Closely)

• CYP2A6 inhibitors (e.g., fluvoxamine): may raise letrozole levels modestly.
• Anticoagulants (e.g., warfarin): monitor INR as estrogen reduction can affect clotting.
• SSRIs affecting platelet function (e.g., fluoxetine): observe for bleeding tendencies.