Generic Name

Tamoxifen

Mechanism

Tamoxifen is a non‑steroidal selective estrogen receptor modulator (SERM).
• Receptor Binding: Competes with estrogen for the estrogen receptor (ER) alpha and beta on breast tissue.
• Antagonist in Mamma‑Carcinoma: Blocks estrogen‑mediated transcription of proliferation genes → decreased breast epithelial cell proliferation.
• Partial Agonist in Vascular/Endometrial Tissue: Increases estrogenic activity in bone and uterus; explains bone‑protective effect and endometrial hyperplasia risk.
• Metabolites: 4‑hydroxytamoxifen (endoxifen) is ~10–20× more potent, formed primarily via CYP2D6; contributes to individual variability in response.

Pharmacokinetics

• Absorption: Oral bioavailability ≈ 79 %. Peak plasma concentrations reached in 2–3 h.
• Distribution: High protein binding (~ 99 %); large volume of distribution (~ 120 L).
• Metabolism: Extensive hepatic metabolism; mainly CYP3A4, CYP2D6, CYP1A2 produce endoxifen and N‑oxide metabolites.
• Elimination: Half‑life ~ 5–7 days for tamoxifen; endoxifen ~ 13–21 days. Excreted mainly via feces (70 %) and urine (20 %).
• Drug Interactions: CYP2D6 inhibitors (e.g., fluoxetine) → ↓ endoxifen → ↓ efficacy; caution with potent CYP3A4 inhibitors/inducers.

Indications

• Adjuvant Therapy: Early‑stage, ER/PR‑positive breast cancer (women & men).
• Metastatic Breast Cancer: When ER‑positive or as part of therapy sequencing.
• Chemoprophylaxis: 5‑year preventive therapy in high‑risk women (5 mg daily).
• Prophylaxis for ovarian cancer risk in BRCA carriers (limited evidence).

Contraindications

• Absolute Contraindications:
• Active or history of thrombo‑embolic disease (deep vein thrombosis, pulmonary embolism, stroke).
• Known hypersensitivity to tamoxifen or excipients.
• Precautions:
• Pregnancy and lactation → teratogenic; use contraception.
• Liver disease → altered metabolism, increased toxicity.
• Concomitant anticoagulants → additive VTE risk.
• Endometrial pathology (hyperplasia, carcinoma) → increased risk of progression.

Dosing

• Take with food to enhance absorption.
• For patients on CYP2D6 inhibitors, consider dose adjustment or alternative agents (e.g., aromatase inhibitor).
• If a dose is missed, take as soon as remembered, but skip if next dose imminent.

Monitoring

• Baseline: CBC, CMP, liver function, lipid panel.
• Every 3–6 months: CBC, CMP, liver enzymes; assess for VTE symptoms.
• Annual: Pelvic exam + transvaginal ultrasound or endometrial sampling in high‑risk patients.
• Endocrine: Monitor estradiol/FSH/SHBG if pre‑menopausal or for endocrine side effects.
• Weight & VO2 max – optional for cardiac monitoring.

Clinical Pearls

1. CYP2D6 Genotyping: Patients with poor‑metabolizer status may have ≥ 2–5× lower endoxifen levels → reduced efficacy. Consider genotype testing in borderline responders.

2. Tamoxifen vs. Aromatase Inhibitors: In post‑menopausal women, aromatase inhibitors often preferred for higher RR reduction; tamoxifen reserved for pre‑menopausal or in case of ARIA.

3. Breast Cancer Survivorship: For women > 50 yr who need extended endocrine therapy, switch to an aromatase inhibitor after 5 years of tamoxifen to reduce endometrial cancer risk.

4. VTE Prevention: In high‑VTE‑risk patients (e.g., prior stroke, hypercoagulable states), consider prophylactic low‑dose aspirin or discuss alternate agents.

5. Endometrial Surveillance: Use a symptom‑driven approach; routine routine screening is debated, but aggressive endometrial biopsies should be performed for abnormal bleeding.

6. Tamoxifen‑Induced Retinopathy: Patients reporting blurred vision or new visual field changes should undergo dilated eye exam promptly; early detection prevents progression.

7. Drug–Drug Interactions: Avoid strong CYP3A4 inducers (e.g., rifampin) that lower tamoxifen levels; avoid strong CYP2D6 inhibitors unless essential, or dose adjust with therapeutic drug monitoring.

8. Pregnancy Test: Ensure negative pregnancy test before initiating therapy; repeat at 3 months if patient is 15–50 yrs.

9. Bioavailability Boosting: Taking tamoxifen with a high‑fat meal increases absorption by ~ 20 % – helpful for patients with malabsorption.

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• *This drug card provides evidence‑based, concise information suitable for medical students and clinicians for quick reference.*