Previous changes

November 2019 — reviewed. A literature search was conducted in November 2019 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. Primary prevention of breast cancer in women at moderate or high risk has been included as a licensed indication for tamoxifen, as per the manufacturer's Summary of Product Characteristics (SPC) and the British National Formulary (BNF). No changes to clinical recommendations have been made. 

December 2014 — reviewed. A literature search was conducted in October 2014 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The scope of the topic has been changed to cover the general prescribing information on tamoxifen, and the topic structure has been changed to reflect this.

November 2012 — minor update. The links to the electronic medicines compendium (emc) website (www.medicines.org.uk) have been updated.

January 2012 — minor update. Added updated information from the manufacturer's Summary of Product Characteristics (SPC) stating that venlafaxine may alter glycaemic control in people with diabetes mellitus. 

October 2008 to February 2009 — this is a new CKS topic. The evidence base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 February 2024.

HTAs (Health Technology Assessments)

No new HTAs since 1 February 2024.

Economic appraisals

No new economic appraisals relevant to England since 1 February 2024.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 February 2024.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 February 2024.

New policies

No new national policies or guidelines since 1 February 2024.

New safety alerts

No new safety alerts since 1 February 2024.

Changes in product availability

No changes in product availability since 1 February 2024.

How is tamoxifen initiated?

• Tamoxifen is always initiated in secondary care by a specialist. However, treatment may be continued and monitored in primary care.
  • For the treatment of breast cancer, the recommended dose is normally 20 mg daily.
    • No additional benefit, in terms of delayed recurrence or improved survival, has been demonstrated with higher doses.
    • Substantive evidence supporting the use of treatment with 30–40 mg per day is not available, although these doses have been used in some women with advanced disease.
  • For the treatment of anovulatory infertility:
    • In women who are menstruating regularly but with anovular cycles, the recommended dose is initially 20 mg taken on days 2, 3, 4, and 5 of the menstrual cycle. If unsatisfactory basal temperature records or poor pre-ovulatory cervical mucus indicate that this initial course of treatment has been unsuccessful, further courses may be given during subsequent menstrual periods, increasing the dose to 40 mg and then 80 mg daily.
    • In women who are not menstruating regularly, the initial course can be started on any day. If no signs of ovulation are demonstrable, a subsequent course of treatment may start 45 days later, with dosage increased as above, or on day 2 of the cycle if menstruation occurs.
  • For the primary prevention of breast cancer in women at moderate to high risk, the recommended dose is 20 mg daily for 5 years.
    • There is insufficient data to support a higher dose or longer period of use.
    • The use of tamoxifen should be as part of a program including regular breast surveillance tailored to the individual woman, taking into account her risk of breast cancer.

What are the contraindications and cautions for tamoxifen?

• Contraindications
  • Pregnancy. Unless used in the treatment of infertility, effective contraception must be used during treatment and for 2 months after stopping. There are reports of miscarriage, birth defects, and fetal deaths following the use of tamoxifen during pregnancy, although no causal relationship has been established. There is a theoretical risk of genital tract malformations. The manufacturer advises that it should not be used during pregnancy.
    • The UK Teratology Information Service has a monograph and patient leaflet on the use of tamoxifen in pregnancy.
  • Breastfeeding — it is not known if tamoxifen is excreted in human milk. The manufacturer states that it is not recommended during breastfeeding. 
  • Thrombotic disease — there is a small increased risk of thrombotic disease associated with tamoxifen treatment. It is, therefore, contraindicated in:
    • Treatment of infertility in women with a personal or family history of idiopathic venous thromboembolism (VTE) or a genetic predisposition to thromboembolism.
    • Primary prevention of breast cancer in women with a history of deep vein thrombosis or pulmonary embolism.
• Cautions
  • Thrombotic disease — there is a small increased risk of thrombotic disease associated with tamoxifen treatment. It should, therefore, be used with caution for:
    • Treatment of breast cancer in women with a personal or family history of idiopathic VTE or a genetic predisposition to thromboembolism.
  • Acute porphyria — may be aggravated by tamoxifen.
  • Premenopausal women — tamoxifen has been associated with reduced bone density in premenopausal women, although it is not known whether this may result in an increased risk of fracture.
    • Premenopausal women taking tamoxifen should be advised regarding measures to maintain bone health.
    • Tamoxifen does not adversely affect bone mineral density in postmenopausal women.
• The possibility of drug interactions with tamoxifen should also be considered.

What are the adverse effects of tamoxifen?

• The most common adverse effects of tamoxifen are hot flushes (reported in about 50% of women), nausea, fluid retention, vaginal bleeding, vaginal discharge, fatigue, and skin rash.
• Other common adverse effects include:
  • Blood and lymphatic system disorders — anaemia.
  • Eye disorders — cataracts and retinopathy.
  • Gastrointestinal disorders — vomiting, diarrhoea, and constipation.
  • Hepatobiliary disorders — changes in liver enzymes and fatty liver.
  • Immune system disorders — hypersensitivity reactions.
  • Musculoskeletal and connective tissue disorders — muscle pain and leg cramps.
  • Neoplasms — uterine fibroids.
  • Nervous system disorders — ischaemic cerebrovascular events, headache, lightheadedness, dizziness, and sensory disturbances (including paraesthesia and distortion of the sense of taste).
  • Reproductive system disorders — pruritus vulvae and endometrial changes (including hyperplasia and polyps).
  • Skin and subcutaneous tissue disorders — alopecia.
  • Vascular disorders — thromboembolic events (including deep vein thrombosis, microvascular thrombosis, and pulmonary embolism).
  • Others — elevated triglycerides.
• Uncommon adverse effects include:
  • Blood and lymphatic system disorders — thrombocytopenia and leukopenia.
  • Eye disorders — visual disturbances.
  • Hepatobiliary disorders — cirrhosis of the liver.
  • Neoplasms — endometrial cancer.
  • Others — pancreatitis, interstitial pneumonitis, and hypercalcaemia (in women with bony metastases).
• Rare adverse effects include:
  • Blood and lymphatic system disorders — neutropenia and agranulocytosis.
  • Eye disorders — corneal changes and optic neuropathy.
  • Hepatobiliary disorders — hepatitis, cholestasis, hepatic failure, hepatocellular injury, and hepatic necrosis.
  • Nervous system disorders — optic neuritis.
  • Neoplasms — uterine sarcoma (mostly malignant mixed Mullerian tumours) and tumour flare.
  • Reproductive system disorders — endometriosis, cystic ovarian swelling, and vaginal polyps.
  • Skin and subcutaneous tissue disorders — angioedema, Steven-Johnson syndrome, cutaneous vasculitis, bullous pemphigoid, erythema multiforme, and cutaneous lupus erythematosus (all very rare).
  • Others — porphyria cutanea tarda (very rare) and radiation recall (very rare).

How should I manage adverse effects associated with tamoxifen?

• If there are symptoms suggestive of a gynaecological cancer, such as abnormal vaginal bleeding or discharge: 
  • See the CKS topic on Gynaecological cancers - recognition and referral for management information.
• If there are symptoms suggestive of thromboembolism, such as pain and swelling in the calf of one leg and sudden breathlessness: 
  • Use the two-level DVT or PE Wells score to assess the probability of deep vein thrombosis (DVT) or pulmonary embolism (PE), and manage accordingly.
  • See the CKS topics on Deep vein thrombosis and Pulmonary embolism for more information.
• For nausea:
  • Advise the woman to take tamoxifen with food or milk, or at night.
  • Advise that although nausea is quite common initially, it usually improves after a few weeks.
• For menopausal symptoms:
  • Provide information on non-hormonal and non-pharmacological treatments, such as antidepressants, vaginal moisturisers and lubricants, cognitive behavioural therapy, and relaxation techniques.
  • See the sections on Managing women with comorbidities and Managing menopausal symptoms without hormone replacement therapy in the CKS topic on Menopause for more information.
• For all other adverse effects of tamoxifen:
  • Manage in primary care (if appropriate) or refer appropriately.

What are the key drug interactions with tamoxifen?

• Possible drug interactions with tamoxifen include:
  • Anastrozole — the use of tamoxifen in combination with anastrozole as adjuvant therapy has not shown improved efficacy compared with tamoxifen alone. 
    • The manufacturer states that concurrent treatment is contraindicated.
  • Cytochrome P450 2D6 (CYP2D6) inhibitors — tamoxifen is a prodrug that is extensively metabolized to more potent active metabolites (the most significant of which is endoxifen) by the liver enzyme CYP450. Inhibition of this enzyme potentially prevents formation of the active compounds, thereby decreasing the efficacy of tamoxifen. 
    • Potent CYP2D6 inhibitors (such as paroxetine, fluoxetine, quinidine, cinacalcet, and bupropion) should be avoided whenever possible during tamoxifen treatment.
    • If new antidepressant treatment is indicated, prescribers could consider those with weak inhibitory effects on CYP2D6, such as citalopram, escitalopram, sertraline, and venlafaxine. 
    • If the woman is on established antidepressant treatment with a potent CYP2D6 inhibitor, the risks of destabilisation of the mental health condition should be included in the overall risk:benefit analysis if a switch of antidepressant is being considered.
  • Hormonal contraceptives — both tamoxifen and oral contraceptives can increase the risk of thromboembolism.
    • Concurrent use is not recommended.
    • In addition, progestogen-only contraception, combined hormonal contraception, and the levonorgestrel intrauterine system (LNG-IUS) are contraindicated in women with current breast cancer due to unacceptable health risks (UKMEC 4), and should only be used after consultation with an expert (UKMEC 3) in women with a history of breast cancer and no evidence of recurrence for 5 years. See the section on Assessment for specific contraceptive methods in the CKS topic on Contraception - assessment for more information.
  • Hormone replacement therapy (HRT) — both tamoxifen and HRT can increase the risk of thromboembolism, and there is some evidence that HRT may reduce the effectiveness of tamoxifen.
    • Concurrent use is not recommended.
    • In addition, HRT is contraindicated in women with current, past, or suspected breast cancer. See the CKS topic on Menopause for more information.
  • Warfarin — tamoxifen enhances the anticoagulant effects of warfarin.
    • In women receiving tamoxifen for the primary prevention of breast cancer, the use of coumarin-type anticoagulants (such as warfarin) is contraindicated.
    • For all other women, monitor international normalized ratio (INR) closely and reduce the dose of warfarin if needed.
• For a complete list of possible drug interactions with tamoxifen, see the electronic Medicines Compendium (eMC) or the British National Formulary (BNF).

What information and advice should I give to a woman taking tamoxifen?

• Advise the woman:
  • To continue taking tamoxifen unless told otherwise by her specialist.
  • There is a small risk of endometrial cancer and thromboembolic disease associated with tamoxifen treatment.
    • She should seek prompt medical attention if she experiences abnormal vaginal bleeding or discharge or symptoms of thromboembolism (such as pain and swelling in the calf of one leg or sudden breathlessness).
  • To seek medical attention if she experiences any other adverse effects associated with tamoxifen treatment, such as gastrointestinal symptoms, visual problems, or skin disorders.
  • To discuss with her consultant if she is scheduled for elective surgery due to the increased risk of thromboembolic events. 
    • For women taking tamoxifen for the primary prevention of breast cancer or the treatment of anovulatory infertility, tamoxifen should be stopped at least 6 weeks before surgery or long-term immobility and restarted only when the woman is fully mobile.
    • For women taking tamoxifen for the treatment of breast cancer, tamoxifen should not be stopped before surgery or long-term immobility unless the risk of tamoxifen-induced thrombosis clearly outweighs the risk of interrupting treatment.
• For a woman of childbearing potential, advise that she should not become pregnant whilst taking tamoxifen or within two months of cessation of tamoxifen treatment.
  • Inform the woman of the potential risks to the fetus should she become pregnant whilst taking tamoxifen or within two months of cessation of tamoxifen treatment. 
    • A Patient information leaflet on Use of tamoxifen in pregnancy is available from the UK Teratology Information Service.
  • She should use barrier or other adequate non-hormonal contraceptive methods if sexually active. See the CKS topic on Contraception - assessment for information on choosing a suitable method of contraception.
  • Advise that she should discuss with her consultant if she wants to attempt to conceive. 
• For premenopausal women taking tamoxifen, advise that tamoxifen has been associated with reduced bone density.
  • Advise on measures to maintain bone health. See the CKS topic on Osteoporosis - prevention of fragility fractures for more information.
• Ensure the woman is aware of the need for periodic monitoring for serious adverse effects of tamoxifen. 
  • This is usually done in secondary care and may include breast and gynaecological examination.
• Provide written information on tamoxifen.
  • A patient information booklet on Tamoxifen is available from Breast Cancer Now.