Generic Name

reversible, non‑steroidal aromatase inhibitor

Mechanism

*Anastrozole* is a reversible, non‑steroidal aromatase inhibitor that competitively binds the heme moiety of the aromatase enzyme (CYP19A1). It irreversibly blocks the conversion of androstenedione and testosterone to estrone and estradiol, thereby suppressing peripheral estrogen synthesis in post‑menopausal women.
• Inhibition is biphasic: an initial rapid binding followed by a slower, more sustained blockade.
• Suppression of estrogen levels (<0.1 pg/mL) is achieved by 1 mg PO daily.
• No direct effect on estrogen receptors; efficacy depends on adequate systemic aromatase inhibition.

Pharmacokinetics

• Administration: Oral, once daily, without a loading dose.
• Absorption: Rapid, with peak plasma concentrations (Cmax) at ~0.5–1 h. Food does not alter bioavailability.
• Half‑life: ~48–65 h (average ~4 days), allowing stable suppression over 24 h.
• Volume of distribution: ~36 L (low lipophilicity).
• Metabolism: Primarily hepatic via *CYP3A4* and *CYP2D6*; extensive first‑pass metabolism, 2–4 metabolites.
• Elimination: ~70 % fecal, ~30 % renal. Renal/hepatic impairment does not markedly alter exposure, but close monitoring is advised.
• Drug interactions: Moderate‐strength inhibitors of CYP3A4/2D6 (e.g., ketoconazole) increase exposure; strong inducers (rifampin) decrease it.

Indications

• Adjuvant therapy: Early‑stage, estrogen‑receptor‑positive breast cancer in post‑menopausal women after surgical or radiologic therapy.
• Metastatic disease: Post‑menopausal women with progressive, estrogen‑dependent breast cancer.
• Clinical trials: Evaluated in combination with bisphosphonates or denosumab for bone preservation.

Contraindications

• Bone health: Estrogen suppression → loss of bone mineral density (BMD); fracture risk ↑.
• Menopausal symptoms: Hot flashes, arthralgia, fatigue.
• Liver impairment: Mild–moderate hepatic dysfunction may lead to accumulation. |

| Precautions |
• Post‑menopausal status verification;
• Use cautiously in patients with pre‑existing osteoporosis;
• Monitor for potential drug interactions with CYP3A4/2D6 modulators. |

Dosing

• Standard dose: 1 mg orally once daily, 30 min before or after a meal.
• Start‑up: No loading dose; steady‑state estrogen suppression occurs after ~2–3 weeks.
• Duration: 5–10 years adjuvant therapy is common; metastatic regimens often 12 h missed.

Adverse Effects

Monitoring

• Baseline:
• CBC, CMP (including AST/ALT, bilirubin)
• Serum lipid profile, fasting glucose
• Bone mineral density (DEXA)
• Serum estradiol (baseline)
• Post‑initiation:
• CBC/CMP every 3 months first year, q6 months thereafter.
• DEXA at 12 months and annually thereafter.
• Clinical evaluation every visit for hot flashes, arthralgia, fracture symptoms.
• Long‑term (≥5 yrs):
• Repeat cholesterol and glucose annually.
• Early discontinuation if BMD loss >12 % or fracture.

Clinical Pearls

• Bone preservation is critical: Combine anastrozole with bisphosphonates (e.g., zoledronic acid) or denosumab in patients ≥65 yrs or with osteoporosis risk factors—reduces fracture incidence by ~30 %.
• “Hot flash” management: Start with low‑dose SSRIs (citalopram 10 mg) or NSAIDs; avoid high‑dose clomiphene, as it partially stimulates estradiol production.
• Renal/hepatic modifiers: Strong CYP induction (rifampin) can lower anastrozole levels by up to 30 %; consider dose adjustment or alternative therapy.
• Re‑initiation after interruption: Anastrozole exposure does not require a loading dose even after months of discontinuation—steady‑state achieved quickly.
• Men & AI Therapy: Off‑label use in men with breast cancer is documented; testosterone supplementation may counteract aromatase inhibition – use cautiously.
• Quality of life: Educate patients that menopausal symptoms (dry eyes, vaginal atrophy) are reversible after completion of therapy; lubricants and local estrogen (topical) can be used when clinically appropriate.
• Screening for compliance: Many patients perceive AI therapy as “once‑daily” with no side‐effects; regular educational follow‑up improves adherence >90 %.

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• Key Takeaway: Anastrozole is a well‑tolerated, potent aromatase inhibitor for post‑menopausal breast cancer patients that requires vigilant bone monitoring and symptom management to maximize efficacy and maintain quality of life.