Pharmacology · Selective oestrogen receptor modulators (SERMs)
Tamoxifen !
A breast cancer tablet that blocks oestrogen in the breast but acts like it in the uterus and bone. It raises the risk of clots and uterine cancer.
Updated 2026-11-01
The figure shows 4-hydroxytamoxifen, an active metabolite of tamoxifen, in the ligand-binding domain of human ERα; its side chain keeps helix 12 out of the active position.
Mechanism of action
Tamoxifen and its active metabolites bind the oestrogen receptor and compete with estradiol. In breast tissue the complex fails to recruit co-activators, so oestrogen-driven genes stay off and receptor-positive tumour cells stop proliferating. In the endometrium, bone and liver it behaves as a partial agonist, which explains endometrial thickening, preserved bone after menopause and changes in clotting factors.
- Liver enzymes form active metabolites
- They bind the oestrogen receptor instead of estradiol
- In the breast the receptor stays inactive: tumour growth stops
- In uterus and bone it acts partly like oestrogen
Pharmacokinetics
- Absorption
- Taken by mouth
- Metabolism
- Liver, by CYP3A, CYP2C9 and CYP2D6, to active metabolites such as N-desmethyltamoxifen
- Elimination
- Mainly in the faeces
- Half-life
- About 5 to 7 days; its main metabolite about 2 weeks
- Onset and duration
- Steady state takes weeks
Indications
- Hormone receptor-positive breast cancer, adjuvant or metastatic, in women and men Breast cancer →
- Ductal carcinoma in situ after surgery and radiation, to lower the risk of invasive cancer Breast cancer →
- Reduction of breast cancer risk in women at high risk Breast cancer →
Adverse effects
Common
- Hot flashes
- Vaginal discharge or bleeding
- Menstrual changes in premenopausal women
- Nausea
- Fluid retention
Contraindications
- Hypersensitivity to tamoxifen
- For risk reduction or ductal carcinoma in situ: history of deep vein thrombosis or pulmonary embolism, or need for coumarin anticoagulants
Key interactions
- Warfarin and other coumarin anticoagulants
- Much stronger anticoagulant effect; prothrombin time is monitored closely.
- Letrozole
- Tamoxifen lowers letrozole levels.
- Anastrozole
- The combination adds no benefit and is not used.
- Cytotoxic chemotherapy
- Higher risk of thromboembolic events.
What is monitored
- Gynaecological checks and any abnormal vaginal bleeding
- Signs of thrombosis: leg swelling, chest pain, shortness of breath
- Eye examination for cataracts
- Blood counts and liver tests periodically
- Calcium in patients with bone metastases
Administration and safety
- Oral tablet or solution, at the same time each day.
- Hazardous drug: handle broken tablets with care, especially during pregnancy.
Nursing care
- Teach the patient to report any abnormal vaginal bleeding, pelvic pain or pressure without delay.
- Teach the signs of a clot and stroke: one swollen or painful leg, chest pain, sudden breathlessness, sudden weakness or speech trouble.
- Ask about warfarin and other anticoagulants before starting.
- Hot flashes are common; report them if they are severe.
- Non-hormonal contraception is needed in premenopausal women.
Pregnancy and breastfeeding
Can cause fetal harm; pregnancy is avoided during treatment and for about two months after, using non-hormonal contraception.
Test yourself
Think of the answer, then tap the question to see it.
Why does tamoxifen raise the risk of endometrial cancer?
It is a partial oestrogen agonist in the endometrium, so it stimulates endometrial growth even while it blocks oestrogen in the breast.
What happens to the INR when tamoxifen is added to warfarin?
The anticoagulant effect increases significantly, so the INR can rise and bleeding becomes more likely; prothrombin time is monitored closely.
Why can tamoxifen be used in premenopausal women while aromatase inhibitors alone cannot?
Tamoxifen blocks the oestrogen receptor whatever the source of oestrogen, including the ovary; aromatase inhibitors alone cannot stop ovarian oestrogen production.
A woman on tamoxifen has sudden pain and swelling in one calf. What should be suspected?
Deep vein thrombosis, a known serious adverse effect of tamoxifen; it needs urgent assessment.
Related drugs
Related conditions
← Back to the class: Selective oestrogen receptor modulators (SERMs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Tamoxifen: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2018); DailyMed - TAMOXIFEN CITRATE tablet (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); HUMAN ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH 4-HYDROXYTAMOXIFEN (RCSB Protein Data Bank, 1999).
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Representative model, for educational purposes only.