Drugs List

Therapeutic Indications

Uses

Advanced prostate cancer
Pituitary desensitisation in preparation for ovulation induction regimes

Administration

For subcutaneous injection only.

Contraindications

Breastfeeding
Hormone dependent neoplasm
Hormone-refractory prostatic cancer
Pregnancy
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Family history of long QT syndrome
Predisposition to long QT syndrome
Predisposition to prolongation of QT interval
Depression
Diabetes mellitus
History of long QT syndrome
History of torsade de pointes
Hypertension
Long QT syndrome
Metabolic bone disease
Polycystic ovarian syndrome
Porphyria

Not effective following surgical removal of testes
Advise patient dizziness may affect ability to drive or operate machinery
Evaluate patients for cardiovascular disease prior to treatment
Not all available brands are licensed for all indications
Prostate cancer: Prophylaxis of flare with anti-androgen is recommended
Treatment to be initiated and supervised by a specialist
Contains benzyl alcohol
Exclude pregnancy prior to initiation of treatment
Monitor plasma testosterone levels before and 3 monthly during treatment
Monitor blood glucose closely in patients with diabetes mellitus
Monitor blood pressure in hypertensive patients
Monitor closely patient with depression
Monitor estradiol and progesterone levels closely during treatment
Monitor for occurrence of anaemia
Monitor patients with cardiovascular conditions
Monitor stimulation cycle
Review treatment if deterioration of cardiovascular disease
Disease flare may occur at beginning of treatment
May increase follicle recruitment in polycystic ovarian syndrome
May precipitate depression
Ovarian cysts can develop in the initial treatment phase
Ovarian hyperstimulation syndrome can occur
Discontinue if no improvement in spite of adequate testosterone suppression
Discontinue if testosterone levels do not reach therapeutic range in 4-6wks
Advise patient to seek medical advice if reaction occurs on self-injection

Caution is required in patients with metabolic bone disease because reduced bone mineral density can occur. Periodically monitor bone mineral density and use preventative measures during therapy to prevent osteopenia/osteoporosis in patients with additional risk factors for osteoporosis, including chronic alcohol abuse, smoking, long term treatment with anticonvulsants or corticosteroids or a family history of osteoporosis.

Pituitary desensitisation prior ovulation induction regimes
The combined use of buserelin and gonadotrophins may constitute a higher risk of ovarian hyperstimulation syndrome (OHSS) than with gonadotrophins alone. Monitor the stimulation cycle carefully to identify patients at risk of developing OHSS, the addition of hCG should be withheld if necessary.

Symptoms of OHSS include:
abdominal pain
abdominal tension
weight gain
ovarian cysts
nausea
vomiting
ovarian enlargement
dyspnoea
diarrhoea
oliguria
haemoconcentration
hypercoagulability

An acute abdomen may occur as a result of pedicle tension or rupture of the ovary. Severe OHSS may result in thromboembolic events, with the possibility of fatal outcomes.

Treatment of prostate cancer
Clinical improvement should become apparent once testosterone levels have begun to fall below their baseline concentration. If testosterone levels do not reach the therapeutic range within 4 to 6 weeks the dosage schedule should be checked to ensure it is being followed exactly. In the unlikely event that a patient receiving the full dose does not show a suppression of testosterone to the therapeutic range, an alternative therapy should be considered.

Following the initial determination of testosterone levels, monitoring should be carried out at 3 monthly intervals. Absence of clinical improvement despite adequate testosterone suppression may be indicative of a tumour that is unresponsive to hormone manipulation. In these circumstances continuing therapy will not yield further benefit and treatment should be discontinued.

Pregnancy and Lactation

Pregnancy

Buserelin is contraindicated in pregnancy.

At the time of writing there is little published information regarding the use of buserelin during pregnancy.

Much of the data concerning the safety of GnRH analogues have not demonstrated serious side effects such as miscarriage, birth defects or foetal growth restriction. However it is suggested GnRH analogues can cross the placenta due to their relatively low molecular weight therefore there is still concern about the effects on the CNS (Schaefer et al, 2015). In several studies the children of pregnant women exposed to GnRH antagonists during pregnancy have shown subsequent neurological development disorders, however Schaefer states although it is not recommended to use GnRH analogues during pregnancy, they are also not contraindicated.

The manufacturer states the use of buserelin is contraindicated during pregnancy and suggests pregnancy must be excluded before starting treatment.

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

Buserelin is contraindicated in breastfeeding.

Buserelin is excreted in breast milk in small quantities. At the time of writing there is limited published information regarding the use of buserelin during breastfeeding. Studies have not shown buserelin to cause harm to breastfed infants, however the manufacturer suggest to avoid the use of buserelin during breastfeeding.

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

Acne
Allergic asthma with dyspnoea
Alopecia
Anaphylactic shock
Anxiety
Arthralgia
Blood lipid changes
Blurred vision
Bone pain (transient)
Breast tenderness
Changes in breast size
Changes in libido
Changes in scalp or body hair
Concentration disturbances
Constipation
Contact lenses may irritate
Decrease in bone mineral density
Decreased glucose tolerance
Decreased glycaemic control in diabetes
Depression
Deterioration in blood pressure in hypertensive patients
Deterioration in general well-being
Diarrhoea
Difficulty in micturition
Disturbances of appetite
Dizziness
Drowsiness
Dry skin
Dryness of eyes
Dyspareunia
Elevation of liver enzymes
Emotional lability
Facial oedema
Feeling of pressure behind the eyes
Headache
Hearing disturbances
Hirsutism
Hot flushes
Hydronephrosis
Hypersensitivity reactions
Increase in alkaline phosphatase
Increased risk of fractures
Increased sweating
Increased thirst
Itching
Lactation
Leucopenia
Local pain (injection site)
Lower abdominal pain
Lymphostasis
Memory disturbances
Menopausal-like symptoms
Migraine-like headache
Mood changes
Musculoskeletal pain
Myalgia
Nausea
Neoplasms
Nervousness
Oedema of the extremities (arms and legs)
Osteoporosis
Ovarian cysts
Ovarian hyperstimulation syndrome (OHSS)
Palpitations
Paraesthesia
Pituitary adenomas
Prolongation of QT interval
Pulmonary embolism
Rash
Rise in the serum testosterone level (transient)
Serum bilirubin increased
Shoulder pain
Skin reddening
Sleep disturbances
Splitting nails
Stiffness
Stomach pain
Testicular atrophy
Thrombocytopenia
Thrombosis
Tinnitus
Tiredness
Tumour flare
Tumour pain
Urticaria
Vaginal bleeding on withdrawal
Vaginal discharge
Vaginal dryness
Vomiting
Weakness of legs
Weight changes
Worsening depression

Presentation

Parenteral formulations of buserelin.

Drugs List

Therapeutic Indications

Uses

Advanced prostate cancer
Pituitary desensitisation in preparation for ovulation induction regimes

Dosage

Adults

Administration

For subcutaneous injection only.

Contraindications

Breastfeeding
Hormone dependent neoplasm
Hormone-refractory prostatic cancer
Pregnancy
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Family history of long QT syndrome
Predisposition to long QT syndrome
Predisposition to prolongation of QT interval
Depression
Diabetes mellitus
History of long QT syndrome
History of torsade de pointes
Hypertension
Long QT syndrome
Metabolic bone disease
Polycystic ovarian syndrome
Porphyria

Not effective following surgical removal of testes
Advise patient dizziness may affect ability to drive or operate machinery
Evaluate patients for cardiovascular disease prior to treatment
Not all available brands are licensed for all indications
Prostate cancer: Prophylaxis of flare with anti-androgen is recommended
Treatment to be initiated and supervised by a specialist
Contains benzyl alcohol
Exclude pregnancy prior to initiation of treatment
Monitor plasma testosterone levels before and 3 monthly during treatment
Monitor blood glucose closely in patients with diabetes mellitus
Monitor blood pressure in hypertensive patients
Monitor closely patient with depression
Monitor estradiol and progesterone levels closely during treatment
Monitor for occurrence of anaemia
Monitor patients with cardiovascular conditions
Monitor stimulation cycle
Review treatment if deterioration of cardiovascular disease
Disease flare may occur at beginning of treatment
May increase follicle recruitment in polycystic ovarian syndrome
May precipitate depression
Ovarian cysts can develop in the initial treatment phase
Ovarian hyperstimulation syndrome can occur
Discontinue if no improvement in spite of adequate testosterone suppression
Discontinue if testosterone levels do not reach therapeutic range in 4-6wks
Advise patient to seek medical advice if reaction occurs on self-injection

Caution is required in patients with metabolic bone disease because reduced bone mineral density can occur. Periodically monitor bone mineral density and use preventative measures during therapy to prevent osteopenia/osteoporosis in patients with additional risk factors for osteoporosis, including chronic alcohol abuse, smoking, long term treatment with anticonvulsants or corticosteroids or a family history of osteoporosis.

Pituitary desensitisation prior ovulation induction regimes
The combined use of buserelin and gonadotrophins may constitute a higher risk of ovarian hyperstimulation syndrome (OHSS) than with gonadotrophins alone. Monitor the stimulation cycle carefully to identify patients at risk of developing OHSS, the addition of hCG should be withheld if necessary.

Symptoms of OHSS include:
abdominal pain
abdominal tension
weight gain
ovarian cysts
nausea
vomiting
ovarian enlargement
dyspnoea
diarrhoea
oliguria
haemoconcentration
hypercoagulability

An acute abdomen may occur as a result of pedicle tension or rupture of the ovary. Severe OHSS may result in thromboembolic events, with the possibility of fatal outcomes.

Treatment of prostate cancer
Clinical improvement should become apparent once testosterone levels have begun to fall below their baseline concentration. If testosterone levels do not reach the therapeutic range within 4 to 6 weeks the dosage schedule should be checked to ensure it is being followed exactly. In the unlikely event that a patient receiving the full dose does not show a suppression of testosterone to the therapeutic range, an alternative therapy should be considered.

Following the initial determination of testosterone levels, monitoring should be carried out at 3 monthly intervals. Absence of clinical improvement despite adequate testosterone suppression may be indicative of a tumour that is unresponsive to hormone manipulation. In these circumstances continuing therapy will not yield further benefit and treatment should be discontinued.

Pregnancy and Lactation

Pregnancy

Buserelin is contraindicated in pregnancy.

At the time of writing there is little published information regarding the use of buserelin during pregnancy.

Much of the data concerning the safety of GnRH analogues have not demonstrated serious side effects such as miscarriage, birth defects or foetal growth restriction. However it is suggested GnRH analogues can cross the placenta due to their relatively low molecular weight therefore there is still concern about the effects on the CNS (Schaefer et al, 2015). In several studies the children of pregnant women exposed to GnRH antagonists during pregnancy have shown subsequent neurological development disorders, however Schaefer states although it is not recommended to use GnRH analogues during pregnancy, they are also not contraindicated.

The manufacturer states the use of buserelin is contraindicated during pregnancy and suggests pregnancy must be excluded before starting treatment.

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

Buserelin is contraindicated in breastfeeding.

Buserelin is excreted in breast milk in small quantities. At the time of writing there is limited published information regarding the use of buserelin during breastfeeding. Studies have not shown buserelin to cause harm to breastfed infants, however the manufacturer suggest to avoid the use of buserelin during breastfeeding.

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

Acne
Allergic asthma with dyspnoea
Alopecia
Anaphylactic shock
Anxiety
Arthralgia
Blood lipid changes
Blurred vision
Bone pain (transient)
Breast tenderness
Changes in breast size
Changes in libido
Changes in scalp or body hair
Concentration disturbances
Constipation
Contact lenses may irritate
Decrease in bone mineral density
Decreased glucose tolerance
Decreased glycaemic control in diabetes
Depression
Deterioration in blood pressure in hypertensive patients
Deterioration in general well-being
Diarrhoea
Difficulty in micturition
Disturbances of appetite
Dizziness
Drowsiness
Dry skin
Dryness of eyes
Dyspareunia
Elevation of liver enzymes
Emotional lability
Facial oedema
Feeling of pressure behind the eyes
Headache
Hearing disturbances
Hirsutism
Hot flushes
Hydronephrosis
Hypersensitivity reactions
Increase in alkaline phosphatase
Increased risk of fractures
Increased sweating
Increased thirst
Itching
Lactation
Leucopenia
Local pain (injection site)
Lower abdominal pain
Lymphostasis
Memory disturbances
Menopausal-like symptoms
Migraine-like headache
Mood changes
Musculoskeletal pain
Myalgia
Nausea
Neoplasms
Nervousness
Oedema of the extremities (arms and legs)
Osteoporosis
Ovarian cysts
Ovarian hyperstimulation syndrome (OHSS)
Palpitations
Paraesthesia
Pituitary adenomas
Prolongation of QT interval
Pulmonary embolism
Rash
Rise in the serum testosterone level (transient)
Serum bilirubin increased
Shoulder pain
Skin reddening
Sleep disturbances
Splitting nails
Stiffness
Stomach pain
Testicular atrophy
Thrombocytopenia
Thrombosis
Tinnitus
Tiredness
Tumour flare
Tumour pain
Urticaria
Vaginal bleeding on withdrawal
Vaginal discharge
Vaginal dryness
Vomiting
Weakness of legs
Weight changes
Worsening depression

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: August 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: Suprefact Injection. Aventis Pharma Limited. Revised February 2015.

Summary of Product Characteristics: Suprecur Injection. Aventis Pharma Limited. Revised February 2015.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 03 August 2017