Drugs List

Therapeutic Indications

Uses

Alternative to chemotherapy for women with ER positive early breast cancer
Breast cancer - advanced
Carcinoma - prostate (if suitable for hormonal manipulation)
Pituitary downregulation prior to superovulation in assisted reproduction
Thinning of uterine endometrium before or instead of surgery
Treatment of endometriosis
Treatment of uterine fibroids prior to surgery

Treatment of prostate cancer where hormonal therapy suitable in the following settings:

Treatment of metastatic prostate cancer.
Treatment of locally advanced prostate cancer instead of surgical castration.
Adjuvant to radiotherapy in patients with high-risk localised or locally advanced prostate cancer.
Neo-adjuvant treatment prior to radiotherapy in patients with high-risk localised or locally advanced prostate cancer.
Adjuvant to radical prostatectomy in patients with locally advanced prostate cancer at high risk of disease progression.

Treatment of advanced breast cancer in pre- and peri-menopausal women where hormonal therapy is suitable.

Treatment of oestrogen receptor (ER) positive early breast cancer as an alternative to chemotherapy in pre- and peri-menopausal women.

In the management of endometriosis to reduce the size and number of endometrial lesions and alleviate pain.

Endometrial thinning prior to endometrial ablation or resection.

In uterine fibroids with iron to raise the blood count of patients with concomitant anaemia prior to surgery.

To induce pituitary downregulation in assisted reproduction in preparation for superovulation.

Unlicensed Uses

Gonadotrophin-dependent precocious puberty

Administration

The implant is injected subcutaneously into the anterior abdominal wall.

Prior to administration the instruction card must be read.

Rotate the injection site to prevent atrophy and nodule formation.

Contraindications

Breastfeeding
Pregnancy
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Children under 18 years
Chronic use of drugs that cause osteoporosis
Family history of long QT syndrome
Females of childbearing potential
Strong family history of osteoporosis
Tobacco smoking
Underweight patients
Chronic alcoholism
Depression
Diabetes mellitus
History of torsade de pointes
Hypertension
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Long QT syndrome
Malnutrition
Metabolic bone disease
Polycystic ovarian syndrome

Concurrent HRT may reduce bone mineral loss
Prostate cancer: Prophylaxis of flare with anti-androgen is recommended
Treatment to be initiated and supervised by a specialist
If spinal cord compression present/develops,use specific standard treatment
Monitor closely men at risk of tumour flare for first month of treatment
Monitor closely patient with depression
Monitor ECG in patients at risk of QT prolongation
Monitor for signs and symptoms of glucose intolerance
Monitor patients at risk of spinal cord compression or urinary obstruction
Monitor patients with pre-existing hypertension
Advise patients to report signs of hypercalcaemia
Disease flare may occur at beginning of treatment
If ureteric obstruction present/develops,use specific standard treatment
May cause loss of bone mineral density
May increase follicle recruitment in polycystic ovarian syndrome
Ovarian hyperstimulation syndrome can occur
Not licensed for use in children under 18 years
Endometriosis: Maximum treatment duration 6 months
Female: Barrier or non-hormonal contraception advised during treatment
Advise patient hyperhidrosis/hot flushes may continue after treatment stops

The use of LHRH agonists may cause a reduction in bone mineral density. Therefore, goserelin should be used with caution when treating patients with metabolic bone disease. Bone mineral density should be monitored.

Patients with injection site injury should be monitored for signs and symptoms of abdominal haemorrhage. Caution should be used when administering to patients with a low BMI and/or patients receiving anticoagulants.

Males

Consideration should be given to the initial use of an anti-androgen (e.g. cyproterone acetate 300 mg daily for three days before and three weeks after commencement of goserelin) at the start of LHRH analogue therapy since this has been reported to prevent the possible sequelae of the initial rise in serum testosterone, which may be associated with the progression of prostate cancer.

Concurrent use of a bisphosphonate may reduce bone mineral loss.

Females

During early treatment vaginal bleeding may occur, usually within the first month. Such bleeding should stop spontaneously, however if this is not the case, the reason should be investigated.

In patients receiving treatment for endometriosis, the addition of hormone replacement therapy, a daily oestrogenic and progestogenic agent, has been shown to reduce bone mineral density loss and vasomotor symptoms.

Goserelin may cause an increase in uterine cervical resistance, dilating the cervix may become more difficult.

Some women may enter the menopause during treatment and not resume menses after completion of therapy.

As with other LHRH agonists, there have been reports of ovarian hyperstimulation syndrome (OHSS), associated with the use of goserelin combination with gonadotrophin. The stimulation cycle should be monitored carefully to identify patients at risk of developing OHSS because its severity and incidence may be dependent on the dose regimen of gonadotrophin. Human chorionic gonadotrophin (hCG) should be withheld, if possible.

Pregnancy and Lactation

Pregnancy

Goserelin is contraindicated in pregnancy.

Studies on the effects of goserelin during human pregnancy are very limited however, and there are concerns about the potential effects of goserelin on the foetus, along with a theoretical risk of spontaneous abortion or foetal abnormality. Most of the clinical data from the use of goserelin in this area do not indicate an association between goserelin and serious adverse effects such as increased miscarriage, birth defects or foetal growth restriction. Concern about its potential effects on the CNS exist however, and there are reports of neurological development disorders in children who were antenatally exposed to goserelin.

Schaefer advises that inadvertent exposure is not grounds for termination or invasive diagnostic procedures.

Animal studies regarding goserelin have shown no evidence of teratogenic potential.

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

Goserelin is contraindicated in breastfeeding.

There is insufficient data concerning the use of goserelin during breastfeeding and it is unknown whether goserelin is excreted in breast milk. Due to its structure and high molecular weight however, it is considered unlikely. Caution is recommended regarding potential loss of milk supply as the effect of goserelin on milk production is unknown.

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

Abdominal discomfort
Acne
Alopecia
Anaphylaxis
Arthralgia
Asthma
Breast swelling
Breast tenderness
Bruising at injection site
Cardiac failure
Changes in breast size
Changes in scalp or body hair
Constipation
Decrease in bone mineral density
Decreased glucose tolerance
Degeneration of fibroids
Depression
Diarrhoea
Dizziness
Dry skin
Erectile dysfunction
Exacerbation of symptoms
Gastro-intestinal disturbances
Gynaecomastia
Headache
Hepatic disorders
Hot flushes
Hypercalcaemia
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypotension
Increase in serum cholesterol (transient)
Increased bone pain (temporary)
Increased sweating
Injection site reactions
Interstitial pneumonia
Leg cramps
Migraine
Mood changes
Myalgia
Myocardial infarction
Nausea
Nervousness
Ovarian cysts
Ovarian hyperstimulation
Paraesthesia
Peripheral oedema
Pituitary adenomas
Pituitary apoplexy
Premature menopause
Prolongation of QT interval
Pruritus
Psychotic disorder
Pulmonary embolism
Rash
Reduced libido
Sleep disturbances
Spinal cord compression
Testicular atrophy
Tiredness
Tumour flare
Tumour pain
Ureteric obstruction
Urticaria
Vaginal bleeding
Vaginal discharge
Vaginal dryness
Vaginitis
Visual disturbances
Voice changes
Vomiting
Weight changes

Presentation

Implant containing 3.6 mg goserelin.

Drugs List

Therapeutic Indications

Uses

Alternative to chemotherapy for women with ER positive early breast cancer
Breast cancer - advanced
Carcinoma - prostate (if suitable for hormonal manipulation)
Pituitary downregulation prior to superovulation in assisted reproduction
Thinning of uterine endometrium before or instead of surgery
Treatment of endometriosis
Treatment of uterine fibroids prior to surgery

Treatment of prostate cancer where hormonal therapy suitable in the following settings:

Treatment of metastatic prostate cancer.
Treatment of locally advanced prostate cancer instead of surgical castration.
Adjuvant to radiotherapy in patients with high-risk localised or locally advanced prostate cancer.
Neo-adjuvant treatment prior to radiotherapy in patients with high-risk localised or locally advanced prostate cancer.
Adjuvant to radical prostatectomy in patients with locally advanced prostate cancer at high risk of disease progression.

Treatment of advanced breast cancer in pre- and peri-menopausal women where hormonal therapy is suitable.

Treatment of oestrogen receptor (ER) positive early breast cancer as an alternative to chemotherapy in pre- and peri-menopausal women.

In the management of endometriosis to reduce the size and number of endometrial lesions and alleviate pain.

Endometrial thinning prior to endometrial ablation or resection.

In uterine fibroids with iron to raise the blood count of patients with concomitant anaemia prior to surgery.

To induce pituitary downregulation in assisted reproduction in preparation for superovulation.

Unlicensed Uses

Gonadotrophin-dependent precocious puberty

Dosage

Adults

Children

Administration

The implant is injected subcutaneously into the anterior abdominal wall.

Prior to administration the instruction card must be read.

Rotate the injection site to prevent atrophy and nodule formation.

Contraindications

Breastfeeding
Pregnancy
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Children under 18 years
Chronic use of drugs that cause osteoporosis
Family history of long QT syndrome
Females of childbearing potential
Strong family history of osteoporosis
Tobacco smoking
Underweight patients
Chronic alcoholism
Depression
Diabetes mellitus
History of torsade de pointes
Hypertension
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Long QT syndrome
Malnutrition
Metabolic bone disease
Polycystic ovarian syndrome

Concurrent HRT may reduce bone mineral loss
Prostate cancer: Prophylaxis of flare with anti-androgen is recommended
Treatment to be initiated and supervised by a specialist
If spinal cord compression present/develops,use specific standard treatment
Monitor closely men at risk of tumour flare for first month of treatment
Monitor closely patient with depression
Monitor ECG in patients at risk of QT prolongation
Monitor for signs and symptoms of glucose intolerance
Monitor patients at risk of spinal cord compression or urinary obstruction
Monitor patients with pre-existing hypertension
Advise patients to report signs of hypercalcaemia
Disease flare may occur at beginning of treatment
If ureteric obstruction present/develops,use specific standard treatment
May cause loss of bone mineral density
May increase follicle recruitment in polycystic ovarian syndrome
Ovarian hyperstimulation syndrome can occur
Not licensed for use in children under 18 years
Endometriosis: Maximum treatment duration 6 months
Female: Barrier or non-hormonal contraception advised during treatment
Advise patient hyperhidrosis/hot flushes may continue after treatment stops

The use of LHRH agonists may cause a reduction in bone mineral density. Therefore, goserelin should be used with caution when treating patients with metabolic bone disease. Bone mineral density should be monitored.

Patients with injection site injury should be monitored for signs and symptoms of abdominal haemorrhage. Caution should be used when administering to patients with a low BMI and/or patients receiving anticoagulants.

Males

Consideration should be given to the initial use of an anti-androgen (e.g. cyproterone acetate 300 mg daily for three days before and three weeks after commencement of goserelin) at the start of LHRH analogue therapy since this has been reported to prevent the possible sequelae of the initial rise in serum testosterone, which may be associated with the progression of prostate cancer.

Concurrent use of a bisphosphonate may reduce bone mineral loss.

Females

During early treatment vaginal bleeding may occur, usually within the first month. Such bleeding should stop spontaneously, however if this is not the case, the reason should be investigated.

In patients receiving treatment for endometriosis, the addition of hormone replacement therapy, a daily oestrogenic and progestogenic agent, has been shown to reduce bone mineral density loss and vasomotor symptoms.

Goserelin may cause an increase in uterine cervical resistance, dilating the cervix may become more difficult.

Some women may enter the menopause during treatment and not resume menses after completion of therapy.

As with other LHRH agonists, there have been reports of ovarian hyperstimulation syndrome (OHSS), associated with the use of goserelin combination with gonadotrophin. The stimulation cycle should be monitored carefully to identify patients at risk of developing OHSS because its severity and incidence may be dependent on the dose regimen of gonadotrophin. Human chorionic gonadotrophin (hCG) should be withheld, if possible.

Pregnancy and Lactation

Pregnancy

Goserelin is contraindicated in pregnancy.

Studies on the effects of goserelin during human pregnancy are very limited however, and there are concerns about the potential effects of goserelin on the foetus, along with a theoretical risk of spontaneous abortion or foetal abnormality. Most of the clinical data from the use of goserelin in this area do not indicate an association between goserelin and serious adverse effects such as increased miscarriage, birth defects or foetal growth restriction. Concern about its potential effects on the CNS exist however, and there are reports of neurological development disorders in children who were antenatally exposed to goserelin.

Schaefer advises that inadvertent exposure is not grounds for termination or invasive diagnostic procedures.

Animal studies regarding goserelin have shown no evidence of teratogenic potential.

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

Goserelin is contraindicated in breastfeeding.

There is insufficient data concerning the use of goserelin during breastfeeding and it is unknown whether goserelin is excreted in breast milk. Due to its structure and high molecular weight however, it is considered unlikely. Caution is recommended regarding potential loss of milk supply as the effect of goserelin on milk production is unknown.

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

Abdominal discomfort
Acne
Alopecia
Anaphylaxis
Arthralgia
Asthma
Breast swelling
Breast tenderness
Bruising at injection site
Cardiac failure
Changes in breast size
Changes in scalp or body hair
Constipation
Decrease in bone mineral density
Decreased glucose tolerance
Degeneration of fibroids
Depression
Diarrhoea
Dizziness
Dry skin
Erectile dysfunction
Exacerbation of symptoms
Gastro-intestinal disturbances
Gynaecomastia
Headache
Hepatic disorders
Hot flushes
Hypercalcaemia
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypotension
Increase in serum cholesterol (transient)
Increased bone pain (temporary)
Increased sweating
Injection site reactions
Interstitial pneumonia
Leg cramps
Migraine
Mood changes
Myalgia
Myocardial infarction
Nausea
Nervousness
Ovarian cysts
Ovarian hyperstimulation
Paraesthesia
Peripheral oedema
Pituitary adenomas
Pituitary apoplexy
Premature menopause
Prolongation of QT interval
Pruritus
Psychotic disorder
Pulmonary embolism
Rash
Reduced libido
Sleep disturbances
Spinal cord compression
Testicular atrophy
Tiredness
Tumour flare
Tumour pain
Ureteric obstruction
Urticaria
Vaginal bleeding
Vaginal discharge
Vaginal dryness
Vaginitis
Visual disturbances
Voice changes
Vomiting
Weight changes

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: April 2014

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Zoladex Implant 3.6mg, AstraZeneca UK Ltd. June 2015.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 September 2017