Tamoxifen

Registered South African indications:

• Breast cancer

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Tamoxifen should be used with caution in women with functioning ovaries
• Tamoxifen is contraindicated in women who require coadministration with coumarin-type anticoagulant therapy or in women with a history of deep-vein thrombosis or pulmonary embolus

Contraindications registered in other jurisdictions

General contraindications (all indications)

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy. Pre-menopausal patients must be carefully examined before treatment for all indications to exclude the possibility of pregnancy
• Coadministration with anastrozole

Treatment for infertility

• Tamoxifen should not be used in patients with a personal or family history of confirmed idiopathic venous thromboembolic events or a known genetic defect

Primary prevention of breast cancer

• Tamoxifen should not be used in women with a history of deep vein thrombosis or pulmonary embolus
• Tamoxifen should not be used in women who require coadministration with coumarin-type anticoagulant therapy

• Breastfeeding (Recommendations in other jurisdictions)
• Obesity
• Surgery
• Immobility
• Suppression of menstruation
• Endometrial changes
• Venous thromboembolism (VTE)
• CYP2D6 poor metabolizers (caucasians)
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: fct, tab

South African registered indications and dosages

Breast cancer

• Oral (fct, tab): 20-40mg dly, either in divided doses twice dly or as a single dose once dly

---

The response rate to tamoxifen in breast cancer treatment is similar to that seen with either oestrogens or androgens

Not established for use in children

Pregnancy

South African recommendations

• Contraindicated
• Tamoxifen must not be administered during pregnancy
• Reports of spontaneous abortions, birth defects, and foetal deaths have been associated with tamoxifen use
• In rodent models, tamoxifen has shown changes in foetal reproductive tract development similar to those caused by oestradiol, ethynyloestradiol, clomiphene, and diethylstilboestrol (DES)
• Some of these changes, especially vaginal adenosis, resemble those observed in young women exposed to DES in utero, who have a risk of 1 in 1000 of developing clear-cell carcinoma of the vagina or cervix. The clinical relevance of these findings in rodents is unknown
• Women of childbearing potential/Contraception in males and female 
  • Women should not become pregnant while taking tamoxifen
  • Use barrier or other non-hormonal contraceptive methods if sexually active
  • Premenopausal women must be examined before treatment to rule out pregnancy
  • Women should be informed of potential risks to the fetus if they become pregnant while taking tamoxifen or within 2 months after stopping therapy

Recommendations in other jurisdictions

• Contraindicated
• Pre-menopausal patients must be carefully examined before treatment for all indications to exclude the possibility of pregnancy
• Tamoxifen must not be administered during pregnancy. There have been a small number of reports of spontaneous abortions, birth defects and foetal deaths after women have taken tamoxifen, although no causal relationship has been established. Reproductive toxicology studies in rats, rabbits and monkeys have shown no teratogenic potential
• In rodent models of foetal reproductive tract development, tamoxifen was associated with changes similar to those caused by oestradiol, ethynyloestradiol, clomiphene and diethylstilboestrol (DES). Although the clinical relevance of these changes is unknown, some of them, especially vaginal adenosis, are similar to those seen in young women who were exposed to DES in-utero and who have a 1 in 1000 risk of developing clear-cell carcinoma of the vagina or cervix. Only a small number of pregnant women have been exposed to tamoxifen. Such exposure has not been reported to cause subsequent vaginal adenosis or clear-cell carcinoma of the vagina or cervix in young women exposed in utero to tamoxifen
• Women of childbearing potential
  • Women should not become pregnant while taking tamoxifen and for nine months after stopping therapy
  • Use barrier or other non-hormonal contraceptive methods if sexually active
  • Premenopausal patients must be examined before treatment to rule out pregnancy
  • Women should be informed of potential risks to the foetus if they become pregnant while taking tamoxifen or within nine months after stopping therapy

Breastfeeding

South African recommendations

• Contraindicated
• Tamoxifen must not be given to breastfeeding women
• It is not known if tamoxifen is excreted in human milk, therefore it is not recommended during breastfeeding

Recommendations in other jurisdictions

• Caution; not recommended
• Limited data suggest that tamoxifen and its active metabolites are excreted and accumulate over time in human milk, therefore the drug is not recommended during breastfeeding. The decision either to discontinue nursing or discontinue tamoxifen should take into account the importance of the drug to the mother

Fertility

South African recommendations

• Tamoxifen does not cause infertility, even in the presence of menstrual irregularity

Recommendations in other jurisdictions

• No information available

• No dose adjustment recommended

• No dose adjustment recommended

• No dose adjustment recommended

Central Nervous System Disorders

• Fatigue
• Ischaemic cerebrovascular events
• Headache
• Light headedness

Cardiovascular Disorders

• Hot flushes

Respiratory Disorders

• Interstitial pneumonitis

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Constipation
• Pancreatitis

Hepatobiliary Disorders

• Changes in hepatic enzymes
• Fatty liver
• Cirrhosis of the liver
• Hepatitis
• Cholestasis
• Hepatic failure
• Hepatocellular injury
• Hepatic necrosis

Genitourinary Disorders

• Suppression of menstruation
• Vaginal bleeding
• Vaginal discharge
• Uterine fibroids
• Endometrial cancer
• Uterine Sarcoma
• Tumour Flare
• Pruritus valvae
• Endometrial changes
• Endometriosis
• Cystic ovarian swelling
• Vaginal polyps

Endocrine and Metabolic Disorders

• Fluid retention
• Elevated triglycerides
• Hypercalcaemia

Musculoskeletal Disorders

• Leg cramp
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Skin Rash
• Alopecia
• Angioedema
• Stevens-Johnson syndrome
• Cutaneous vasculitis
• Bullous pemphigoid
• Erythema multiforme
• Porphyria cutanea tarda
• Cutaneous lupus erythematosus

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Thrombocytopenia
• Leukopenia
• Neutropenia
• Agranulocytosisa
• Venous thromboembolism (VTE)
• Hypersensitivity reactions

Sensory Disorders

• Cataracts
• Retinopathy
• Optic neuritis
• Visual disturbances
• Corneal changes
• Optic neuropathy

• Coumarin-type anticoagulants
• Warfarin
• Cytotoxic agents
• Anastrazole
• CYP3A4 inducers
• CYP2D6 inhibitors
• Selective serotonin reuptake inhibitors

• Full blood count
• Bone mineral density in premenopausal women

Additional warning

• Prescribers should obtain careful histories with respect to the patient's personal and family history of VTE

Tamoxifen is a nonsteroidal agent that binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes. The prolonged binding of tamoxifen to the nuclear chromatin of these results in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptake, and decreased estrogen response. It is likely that tamoxifen interacts with other coactivators or corepressors in the tissue and binds with different estrogen receptors, ER-alpha or ER-beta, producing both estrogenic and antiestrogenic effects.

Tablet 10mg

• Neophedan (Pharmacare)

Tablet 20mg

• Kessar (Pfizer) originator
• Neophedan (Pharmacare)
• Nolvadex-D (AstraZeneca) originator
• Tamoxihexal (Sandoz)
• Tamoplex (Teva Pharmaceuticals)