Aromasin
Aromasin
Generic Name
Aromasin
Brand Names
for the potent, potent, steroidal aromatase inhibitor letrozole. It is widely used in hormone‑responsive breast cancer management, particularly in post‑menopausal women, to reduce circulating estrogen levels.
Mechanism
- Selective, irreversible inhibition of the aromatase enzyme (CYP19A1), preventing conversion of adrenal androgens to estrogens.
- Resultant drop in bioavailable estradiol (E₂) suppresses estrogen‐dependent tumor growth.
- Pharmacologically mimics physiological menopause; lowers serum estrogen by up to 90% compared with baseline.
Pharmacokinetics
- Administration: Oral tablet, typically 2.5 mg once daily.
- Absorption: Rapid, peak plasma conc. ~3–5 h after dosing; highly bioavailable (>75 %).
- Distribution: Extensive tissue distribution, plasma protein binding ~88 %.
- Metabolism: Primarily CYP2A6-mediated N‑oxidation; minor contributions from CYP3A4/5.
- Half‑life: ~2 days (t₁/₂ ≈ 122 h); steady state reached in ~2–3 weeks.
- Excretion: Main routes—fecal (≈65 %) and urinary (≈30 %) metabolites.
Indications
- Early‑stage, hormone‑receptor‑positive breast cancer in post‑menopausal women:
- Adjuvant therapy after surgery ± radiation ± chemo.
- Neoadjuvant therapy to reduce tumor size pre‑op.
- Advanced/metastatic breast cancer refractory to tamoxifen:
- As first‑line aromatase inhibitor or after progression on other agents.
Contraindications
- Hypersensitivity to letrozole, letrozole metabolites, or excipients.
- Pregnancy (teratogenic); contraindicated in lactation (drug shows limited excretion in breast milk).
- Active, uncontrolled osteoporosis or significant bone loss—use with caution; often requires bisphosphonate/denosumab co‑therapy.
- Severe hepatic dysfunction: dose reduction/monitoration; letrozole is primarily hepatically cleared.
- Potential drug interactions: potent CYP2A6 inhibitors (e.g., *clopidogrel*) or inducers (e.g., *rifampin*) can alter trough levels.
Dosing
- Adjuvant therapy (post‑menopausal): 2.5 mg orally once daily for 5 years (± 5 years extension considered in high‑risk patients).
- Neoadjuvant or metastatic setting: 2.5 mg daily, often combined with CDK4/6 inhibitors or targeted therapies.
- Premenopausal patients: letrozole rarely used alone; combination of ovarian suppression + letrozole may be indicated.
> Note: Starting dose in the adjuvant setting is 2.5 mg, but some regimens initiate at 2 mg for patients with hepatic impairment; titrate based on tolerance.
Adverse Effects
Common (≥ 10 % incidence)
• Hot flashes, night sweats
• Joint pain / arthralgia (often distal extremities)
• Fatigue and headache
• Osteopenia/osteoporosis (due to estrogen reduction)
• Mild constipation, nausea
Serious (≤ 1 % incidence)
• Severe bone demineralization → fracture
• Cardiovascular events (myocardial infarction, stroke; risk amplified with underlying CAD)
• Hepatotoxicity (elevated transaminases); monitor LFTs.
• Rare agranulocytosis, rash, or hypersensitivity reactions.
Monitoring
| Parameter | Frequency | Rationale |
| Liver function tests (AST/ALT/Bilirubin) | Baseline, every 3 months for the first year, then every 6–12 months | Detect hepatotoxicity |
| Bone mineral density (DEXA) | Baseline, annually thereafter | Prevent osteoporosis |
| Serum estradiol | Optional; at baseline and after 3–6 months | Verify suppression |
| Complete blood count | Baseline, every 3 months during first year | Check for hematologic toxicity |
| Vascular assessment | Baseline for patients with CAD risk factors; periodic review | Mitigate CV events |
| Symptom diary (hot flashes, joint pain) | Ongoing | Guide supportive care |
Clinical Pearls
- “Letrozole ≈ *hot‑flash relief* + *bone protection strategy.” Pair letrozole with bisphosphonates or denosumab to offset estrogen‑loss‑induced bone loss, especially in high‑risk post‑menopausal patients.
- “Switch to letrozole after tamoxifen failure.” If a patient relapses on tamoxifen for metastatic disease, starting letrozole (± CDK4/6 inhibitor) can reverse resistance by a different blockade of estrogen signaling.
- “Timing matters.” In neoadjuvant therapy, letrozole’s rapid decline in estrogen levels can reduce tumor volume as early as 4–6 weeks; monitor clinical response early to tailor adjuvant plan.
- “Watch the liver.” Though rare, letrozole is hepatically processed. Prior hepatic impairment warrants liver function monitoring and possible dose adjustment.
- “Bone‑protective first.” Consider prophylactic bisphosphonate therapy immediately upon initiation of aromatase inhibition—especially if baseline DEXA shows osteopenia.
--
• Key takeaways:
• *Letrozole (Aromasin)* is a first‑line aromatase inhibitor in post‑menopausal, hormone‑receptor‑positive breast cancer.
• It reduces estrogen production by >90 % via irreversible aromatase inhibition.
• Dosing is simple (2.5 mg daily), but requires careful bone and hepatic surveillance.
• Pairing with bisphosphonate/denosumab mitigates bone loss; consider switching to letrozole after tamoxifen failure in metastatic disease.