Drugs List

Therapeutic Indications

Uses

Carcinoma of breast

Adjuvant treatment of oestrogen-receptor positive early breast cancer.
Treatment of oestrogren-receptor positive locally advanced or metastatic breast cancer.

Unlicensed Uses

Breast cancer (women at moderate to high risk): Primary prevention
Gynaecomastia
Infertility - female - anovulatory

Treatment of breast cancer.
Anovulatory infertility.
Prevention of breast cancer in women at moderate to high risk.

Contraindications

Children under 18 years
Breastfeeding
Hereditary fructose intolerance
Porphyria
Pregnancy

Precautions and Warnings

Family history of venous thromboembolism
Predisposition to venous thromboembolism
Alcoholism
Epileptic disorder
Hepatic impairment
History of thromboembolic disorder

Advise ability to drive/operate machinery may be affected by side effects
Consider use of anticoagulant prophylaxis if at risk of thromboembolism
Contains alcohol
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Exclude pregnancy prior to initiation of treatment
Monitor ophthalmic function before and during long-term use
Perform a complete physical and gynaecological examination before therapy
If visual disturbances occur, perform ophthalmic evaluation
Investigate if abnormal vaginal bleeding, pain or discharge occurs
Monitor blood values and liver function regularly
Monitor serum calcium levels
Monitor serum triglyceride concentration
Patient should have regular physical and gynaecological examinations
Advise patient of thromboembolic symptoms and to report them if they occur
Increased risk of venous thromboembolism
Menstruation is suppressed in some pre-menopausal women during treatment
Suspend if venous thromboembolism develops
Advise patient not to take St John's wort concurrently
Female: Non-hormonal contraception required until 2 months after treatment
Advise patients risk of endometrial cancer and to report relevant symptoms

An increased incidence of endometrial changes (including hyperplasia, polyps, cancer and uterine sarcoma) have been reported in association with tamoxifen use. Any patient who reports abnormal gynaecological symptoms (such as vaginal bleeding, menstrual irregularities, vaginal discharge and pelvic pain or pressure) should be promptly investigated.

Patients with bony metastases are at an increased risk of hypercalcaemia.

A 2 to 3 fold increase in the risk of developing venous thromboembolism has been shown in healthy women receiving tamoxifen.

Patients may restart tamoxifen when fully mobile. Patients undergoing surgery and subsequent immobility should only stop tamoxifen if the risk of thrombosis outweighs the risk associated with interrupting treatment. Patients should receive appropriate prophylactic measures to prevent thrombosis.

A personal and family history of venous thromboembolism should be determined in breast cancer patients. Screen patients showing prothrombotic risk factors for thrombophilic factors; patients who test positive should be counselled on the risk of thromobosis.

Discontinue tamoxifen immediately if patient presents with venous thromboembolism, and initiate appropriate treatment. Treatment should only be restarted after additional risk assessment.

Pregnancy and Lactation

Pregnancy

Tamoxifen is contraindicated in pregnancy.

The manufacturers contraindicate the use of tamoxifen during pregnancy, citing a small number of reports of spontaneous abortions, birth defects and foetal deaths.

Animal studies showed no teratogenic potential, but intrauterine growth restriction, abortions and premature delivery have been noted in some species.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Tamoxifen is contraindicated in breastfeeding.

It is not known if tamoxifen is excreted in human milk. The manufacturers contraindicate tamifoxen's use in breastfeeding.

LactMed states that tamoxifen can inhibit lactation, and should be avoided in nursing mothers.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal vaginal bleeding
Agranulocytosis
Alopecia
Alterations in hepatic enzymes
Anaemia
Angioedema
Blindness
Bone pain
Bullous pemphigoid
Cataracts
Cholestasis
Corneal changes
Deep vein thrombosis (DVT)
Endometrial hyperplasia
Endometrial polyps
Endometriosis
Erythema multiforme
Fluid retention
Headache
Hepatic disorders (fatty changes)
Hepatic necrosis
Hepatitis
Hot flushes
Hypercalcaemia
Hypersensitivity reactions
Hypertriglyceridaemia
Interstitial pneumonitis
Leg cramps
Leucopenia
Light-headedness
Menstrual disturbances
Nausea
Neutropenia
Optic neuritis
Optic neuropathy
Pancreatitis
Pancytopenia
Pruritus vulvae
Pulmonary embolism
Rash
Retinopathy
Reversible cystic ovarian swellings
Risk of endometrial carcinoma
Stevens-Johnson syndrome
Thrombocytopenia
Thromboembolic disorders
Tumour flare
Tumour pain
Uterine fibroids
Uterine sarcoma
Vaginal discharge
Visual disturbances
Vomiting

Presentation

Oral solution formulations of tamoxifen.

Drugs List

Therapeutic Indications

Uses

Carcinoma of breast

Adjuvant treatment of oestrogen-receptor positive early breast cancer.
Treatment of oestrogren-receptor positive locally advanced or metastatic breast cancer.

Unlicensed Uses

Breast cancer (women at moderate to high risk): Primary prevention
Gynaecomastia
Infertility - female - anovulatory

Treatment of breast cancer.
Anovulatory infertility.
Prevention of breast cancer in women at moderate to high risk.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Contraindications

Children under 18 years
Breastfeeding
Hereditary fructose intolerance
Porphyria
Pregnancy

Precautions and Warnings

Family history of venous thromboembolism
Predisposition to venous thromboembolism
Alcoholism
Epileptic disorder
Hepatic impairment
History of thromboembolic disorder

Advise ability to drive/operate machinery may be affected by side effects
Consider use of anticoagulant prophylaxis if at risk of thromboembolism
Contains alcohol
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Exclude pregnancy prior to initiation of treatment
Monitor ophthalmic function before and during long-term use
Perform a complete physical and gynaecological examination before therapy
If visual disturbances occur, perform ophthalmic evaluation
Investigate if abnormal vaginal bleeding, pain or discharge occurs
Monitor blood values and liver function regularly
Monitor serum calcium levels
Monitor serum triglyceride concentration
Patient should have regular physical and gynaecological examinations
Advise patient of thromboembolic symptoms and to report them if they occur
Increased risk of venous thromboembolism
Menstruation is suppressed in some pre-menopausal women during treatment
Suspend if venous thromboembolism develops
Advise patient not to take St John's wort concurrently
Female: Non-hormonal contraception required until 2 months after treatment
Advise patients risk of endometrial cancer and to report relevant symptoms

An increased incidence of endometrial changes (including hyperplasia, polyps, cancer and uterine sarcoma) have been reported in association with tamoxifen use. Any patient who reports abnormal gynaecological symptoms (such as vaginal bleeding, menstrual irregularities, vaginal discharge and pelvic pain or pressure) should be promptly investigated.

Patients with bony metastases are at an increased risk of hypercalcaemia.

A 2 to 3 fold increase in the risk of developing venous thromboembolism has been shown in healthy women receiving tamoxifen.

Patients may restart tamoxifen when fully mobile. Patients undergoing surgery and subsequent immobility should only stop tamoxifen if the risk of thrombosis outweighs the risk associated with interrupting treatment. Patients should receive appropriate prophylactic measures to prevent thrombosis.

A personal and family history of venous thromboembolism should be determined in breast cancer patients. Screen patients showing prothrombotic risk factors for thrombophilic factors; patients who test positive should be counselled on the risk of thromobosis.

Discontinue tamoxifen immediately if patient presents with venous thromboembolism, and initiate appropriate treatment. Treatment should only be restarted after additional risk assessment.

Pregnancy and Lactation

Pregnancy

Tamoxifen is contraindicated in pregnancy.

The manufacturers contraindicate the use of tamoxifen during pregnancy, citing a small number of reports of spontaneous abortions, birth defects and foetal deaths.

Animal studies showed no teratogenic potential, but intrauterine growth restriction, abortions and premature delivery have been noted in some species.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Tamoxifen is contraindicated in breastfeeding.

It is not known if tamoxifen is excreted in human milk. The manufacturers contraindicate tamifoxen's use in breastfeeding.

LactMed states that tamoxifen can inhibit lactation, and should be avoided in nursing mothers.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Advise patient risk of endometrial cancer and to report relevant symptoms

Advise patient of thromboembolic symptoms, including calf pain or breathlessness, and to report them if they occur.

Advise patient receiving, or having previously received, tamoxifen to report immediately any abnormal gynaecological symptoms such as menstrual irregularities, vaginal discharge or bleeding, pelvic pain or pressure suggestive of endometrial changes.

Advise breast cancer patients to use barrier or other non-hormonal methods of contraception during treatment and for 2 months thereafter and inform them of the possible risks to the foetus should they become pregnant during treatment.

Advise patient that dizziness and fatigue may initially affect ability to drive.

Advise patient not to take St John's wort concurrently.

Side Effects

Abnormal vaginal bleeding
Agranulocytosis
Alopecia
Alterations in hepatic enzymes
Anaemia
Angioedema
Blindness
Bone pain
Bullous pemphigoid
Cataracts
Cholestasis
Corneal changes
Deep vein thrombosis (DVT)
Endometrial hyperplasia
Endometrial polyps
Endometriosis
Erythema multiforme
Fluid retention
Headache
Hepatic disorders (fatty changes)
Hepatic necrosis
Hepatitis
Hot flushes
Hypercalcaemia
Hypersensitivity reactions
Hypertriglyceridaemia
Interstitial pneumonitis
Leg cramps
Leucopenia
Light-headedness
Menstrual disturbances
Nausea
Neutropenia
Optic neuritis
Optic neuropathy
Pancreatitis
Pancytopenia
Pruritus vulvae
Pulmonary embolism
Rash
Retinopathy
Reversible cystic ovarian swellings
Risk of endometrial carcinoma
Stevens-Johnson syndrome
Thrombocytopenia
Thromboembolic disorders
Tumour flare
Tumour pain
Uterine fibroids
Uterine sarcoma
Vaginal discharge
Visual disturbances
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: October 2018

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Tamoxifen Last revised: 10 March 2015
Last accessed: 24 October 2018

Summary of Product Characteristics: Tamoxifen rosemont 10 mg/5 ml Oral Solution. Rosemont Pharmaceuticals Ltd. Revised July 2016

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 24 October 2018

The Welsh Medicines Information Centre (WMIC) Porphyria Information Service.
Available at: https://www.wmic.wales.nhs.uk/porphyria_info.php
Last revised: 03 May 2018
Last accessed: 24 October 2018