Generic Name

Anastrozole

Mechanism

• Anastrozole is a potent, selective, non‑steroidal aromatase inhibitor.
• It irreversibly binds the aromatase (CYP19A1) enzyme, preventing the conversion of androgens to estrogen.
• Resulting in a ~95 % reduction in circulating estrogen levels in post‑menopausal women, diminishing growth stimulus for ER‑positive breast cancer cells.

Pharmacokinetics

• Absorption: ~80 % oral bioavailability; peak plasma concentration (Tmax) at 4‑5 h.
• Distribution: highly lipophilic; protein binding ~90 %.
• Metabolism: hepatic oxidation via CYP2C9 and CYP3A4; active metabolites contribute to pharmacologic activity.
• Elimination: ~40 % renal, 60 % fecal.
• Half‑life: ~14‑22 h, supporting once‑daily dosing.
• Drug interactions: minimal clinically relevant interactions; caution with potent CYP2C9 inhibitors or inducers (e.g., fluconazole, rifampin).

Indications

• Adjuvant therapy for estrogen‑receptor (ER) or progesterone‑receptor (PR)‑positive breast cancer in post‑menopausal women.
• Neoadjuvant use for down‑staging locally advanced, ER‑positive tumors (in select settings).
• Maintains endocrine therapy for oligometastatic disease in ER‑positive, aromatase‑sensitive tumors.

Contraindications

• Hypersensitivity to anastrozole or excipients.
• Pregnancy and lactation: contraindicated; avoid use.
• Severe hepatic impairment: caution; monitor function.
• Osteoporosis or significant bone loss risk: consider baseline bone mineral density assessment.
• History of thromboembolic events: use with caution; absolute contraindication in uncontrolled clotting disorders.

Dosing

• Standard dose: 1 mg orally once daily.
• Duration: typically 5 yrs for adjuvant therapy; individualized for metastatic settings.
• Administration tips: take on an empty stomach or with food to enhance absorption; no need to split tablets.
• Compliance monitoring: monthly to quarterly medication refill checks; patient education on the importance of adherence to reduce recurrence risk.

Adverse Effects

• Osteoporotic risk is dose‑time dependent; cumulative estrogen deprivation worsens bone turnover.
• Cardiotoxicity: rare but documented; patients with baseline cardiovascular risk factors should be monitored.

Monitoring

• Baseline:
• Bone mineral density (DXA), serum calcium, phosphate, alkaline phosphatase.
• Liver function tests (ALT/AST, bilirubin).
• Lipid profile.
• Full blood count.
• Ongoing:
• Every 6 months: bone density, liver enzymes, lipid panel.
• Annually: cardiovascular risk assessment (blood pressure, ECG if indicated).
• Adverse effect surveillance: prompt evaluation for new fractures, cardiac symptoms, or significant fatigue.

Clinical Pearls

• Bone health synergy: Pair aromatase inhibitors with bisphosphonates or denosumab in patients ≥5 yrs to counteract estrogen‑deprivation bone loss.
• Switching strategy: If hot flashes or arthralgia are intolerable, switch to a tamoxifen‑based regimen, especially if prior tamoxifen exposure was well tolerated.
• Early monitoring: Obtain baseline bone density within 3 months of initiation; a decline > 5 % predicts fracture risk.
• Lifestyle adjuncts: Encourage calcium (≥ 1000 mg/d) and vitamin D (≥ 800 IU/d) supplementation, weight‑bearing exercise, and smoking cessation to bolster bone integrity.
• Adherence impact: Non‑adherence reduces recurrence‑free survival by ~ 30 %; simple pill‑box reminders can significantly improve compliance among young post‑menopausal patients.