Drugs List

Therapeutic Indications

Uses

Acromegaly : Symptomatic relief
Hyperprolactinaemia
Infertility - female
Lactation - suppression of
Management of menstrual symptoms
Parkinson's disease
Prolactinoma

Inhibition/suppression of puerperal lactation for medical reasons (not recommended for routine suppression of lactation or relief of post partum pain and engorgement).

Treatment of hyperprolactinaemia in males and females with hypogonadism and/or galactorrhoea.

Treatment of menstrual disorders including polycystic ovary syndrome, amenorrhea and oligomenorrhoea, with or without galactorrhoea.

Drug-induced hyperprolactinaemic disorders.

Treatment of hyperprolactinaemic infertility (bromocriptine has also been used in the treatment of female infertility without hyperprolactinaemia).

Treatment of prolactinoma (specialist use only). Bromocriptine mesilate can be considered the first line treatment of macro-adenomas, and as an alternative to the surgical procedure, transphenoidal hypophysectomy, in patients with micro-adenomas.

Adjunctive treatment with surgery and/or radiotherapy to reduce circulating growth hormone in acromegaly (specialist use only).

Treatment of idiopathic Parkinson's disease either alone or in combination with levodopa.

Contraindications

Children under 7 years
Breastfeeding
Cardiac valvulopathy
Eclampsia
Galactosaemia
History of severe cardiovascular disorder
History of severe psychiatric disorder
Porphyria
Pre-eclampsia
Pregnancy-induced hypertension
Severe cardiovascular disorder
Severe psychiatric disorder
Uncontrolled hypertension

Precautions and Warnings

Children aged 7 to 17 years
History of fibrotic disorder
History of serosal inflammatory disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of peptic ulcer
Hypertension
Lactose intolerance
Pituitary neoplasm
Pregnancy
Raynaud's syndrome

Corticosteroid cover required in adrenal insufficiency
Advise patient hypotension may affect ability to drive or operate machinery
Advise patient somnolence may affect ability to drive or operate machinery
Advise patient that sudden onset sleep episodes may affect ability to drive
Consider stopping diuretic 2-3 days prior to therapy if appropriate
In pituitary tumours, treat the underlying condition
Contains lactose
Baseline assessment of inflammatory markers/ESR advised
Baseline assessment of lung function advised
Evaluate pituitary function before initiating long term therapy
Monitor visual field status before and during treatment
Perform chest X-ray prior to and periodically during treatment
Annual gynaecological assessment in women with regular menstruation
Discontinue if signs of gastro-intestinal bleeding occur
Monitor blood pressure especially at the start of treatment
Monitor for signs of pituitary tumour expansion
Monitor for signs of retroperitoneal fibrosis in Parkinsonian patients
Monitor patients for impulse control disorders
Monitor renal function especially during the initial phase of treatment
Six monthly gynaecological assessment in postmenopausal women
Advise patient to report new visual problems and symptoms
Advise patients to report signs or symptoms of gastro-intestinal ulcer
Dopamine agonists have been associated with pathological gambling
Investigate occurrence of visual disturbance or severe headache
May cause fibrotic changes
Avoid abrupt withdrawal
Advise patient to seek advice at first indications of pregnancy
Discontinue if headaches occur
Discontinue if hypertension develops
Discontinue or reduce dose if CNS toxicity occurs
Discontinue treatment if fibrotic or serosal inflammatory changes occur
If evidence of tumour expansion appears, consider alternative procedures
Reduce dose or discontinue if sudden onset of sleep during daily activities
Not licensed for all indications in all age groups
Advise patient to avoid alcohol during treatment
Female: Contraception required if pregnancy not desired
Breastfeeding: Do not breastfeed if lactation suppression fails

Hyperprolactinaemia may be idiopathic, drug-induced or due to hypothalamic or pituitary disease. The possibility of a pituitary tumour should be investigated, prior to the initiation of bromocriptine. Although bromocriptine will lower prolactin levels in patients with pituitary tumours, treatment with radiotherapy or surgery is still required for the underlying condition.

If pregnancy occurs during bromocriptine therapy for pituitary adenoma, careful monitoring is essential as prolactin-secreting adenomas may expand during pregnancy compressing the optic or other cranial nerves and necessitating emergency surgery.

Visual field impairment is a known complication of macro-prolactinoma. Effective treatment with bromocriptine should restore vision. However, some patients may experience a secondary deterioration of visual fields despite prolactin levels corrected by bromocriptine therapy. A reduction in the dose of bromocriptine may be required if secondary visual impairment occurs. It is essential to monitor visual fields in patients with macro-prolactinomas, to enable early diagnosis of visual impairment and corrective action.

Women being treated with bromocriptine for reasons other than hyperprolactinaemia should be treated with the lowest effective dose to avoid suppression of prolactin below normal levels, with subsequent impairment of luteal function.

Bromocriptine is an ergot derivative. Fibrotic and serosal inflammatory disorders such as pleuritis, pleural and pericardial effusion, pleural and pulmonary fibrosis, constrictive pericarditis, and retroperitoneal fibrosis have occurred after prolonged use of ergot derivatives. Patients with Parkinson's disease with a history of any of these conditions should not be treated with bromocriptine, unless the potential benefit outweighs the risk. The risk of fibrosis with bromocriptine is increased at high doses for long periods of time.
Attention should be paid to the signs and symptoms of;
- Pleuro-pulmonary disease such as dyspnoea, shortness of breath, persistent cough or chest pain.
- Renal insufficiency or ureteral/abdominal vascular obstruction that may occur with pain in the loins/flank and lower limb oedema, as well as any possible abdominal masses or tenderness that may indicate retroperitoneal fibrosis.
- Cardiac failure, as this can be a manifestation of constrictive pericarditis. If cardiac failure occurs, constrictive pericarditis should be excluded.

Some brands contain disodium edetate.

Pregnancy and Lactation

Pregnancy

Bromocriptine has been used throughout pregnancy and there have been a number of studies (more than 2000 pregnancies) into bromocriptine's possible effects on pregnancy. These studies reported a slight increase in the rate of early miscarriage. The incidence of congenital defects reported was 3.5%, this was considered similar to the expected rate in the general population. Long term studies on 213 children followed up to 6 years of age have shown normal mental and physical development. During pregnancy rapid expansion of pituitary tumours sometimes occurs. The manufacturers suggest that, due to the lack of evidence of a link to teratogenic effects, patients who have large tumours, or experience tumour expansion should receive bromocriptine treatment. Schaefer, Peters & Miller (2007) suggest that bromocriptine is the first line treatment for hyperprolactinaemic amenorrhoea, that bromocriptine should be discontinued after conception however continuing treatment is not grounds for termination of pregnancy or invasive diagnostic procedures. Schaefer, Peters & Miller (2007) suggest that patients, who experience ophthalmological complications in connection with macro-prolactinoma, should receive bromocriptine treatment. Overall, bromocriptine should be used with caution in pregnancy, and the mother closely monitored for side effects and avoided if possible.

Treatment with bromocriptine will result in ovulation in female patients. Patients who do not wish to conceive should be advised to use effective contraception, noting that oral contraceptives have been reported to increase serum prolactin levels.

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 14-17 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 ).

Licensed in pregnancy? - No.

Recommended for use in pregnancy? - Yes, for the treatment of large or expanding pituitary tumours and ophthalmological complications of macro-prolactinoma.

Known human teratogen? - No.

Other information - Bromocriptine treatment will result in ovulation in female patients. Patients who do not want to conceive should use effective contraception, noting that oral contraceptives have been reported to increase serum prolactin levels.

Lactation

Bromocriptine should not be used while breastfeeding. Bromocriptine suppresses lactation and therefore is contraindicated while breastfeeding. A number of reports from mothers have not reported any adverse effects. However, maternal deaths have been reported due to cerebrovascular and cardiovascular events and seizures, as a side effect of bromocriptine. Patients given bromocriptine produce milk with higher protein constituents similar to those of colostrum. Schaeffer, Peters & Miller (2007) and Hale (2006) suggest that the prolactin inhibitor cabergoline is the preferred drug for suppression of lactation in nursing mothers. Bromocriptine should not be used while breastfeeding. Patients should avoid breastfeeding for 5 days if bromocriptine has failed to suppress lactation.

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

Drug excreted in breast milk? - Unknown.

Considered suitable or recommended by the manufacturer? - No, contraindicated.

Drug substance licensed in infants? - No.

Drug known to affect lactation? - Yes, bromocriptine suppresses lactation. Milk produced by mother receiving bromocriptine has a higher than normal protein content.

Side Effects

Abdominal pain
Allergic skin reactions
Alopecia (transient)
Arrhythmias
Binge eating
Blurred vision
Bradycardia
Cardiac valvulopathy
Collapse
Confusion
Constipation
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dyskinesia
Dyspnoea
Exacerbation of Raynaud's disease
Fatigue
Gastro-intestinal ulceration and bleeding
Hallucinations
Headache
Hypersexuality
Hypertension
Hypotension
Increased libido
Insomnia
Leg cramps
Myocardial infarction
Nasal congestion
Nausea
Neuroleptic malignant syndrome-like effect
Paraesthesia
Pathological gambling
Pericardial effusion
Pericarditis
Peripheral oedema
Pleural effusion
Pleural fibrosis
Pleuritis
Postural hypotension
Psychiatric disorders
Psychomotor excitation
Psychosis
Pulmonary fibrosis
Retroperitoneal fibrosis
Seizures
Somnolence
Stroke
Sudden sleep onset episodes
Tachycardia
Tinnitus
Visual disturbances
Vomiting
Withdrawal symptoms

Presentation

Oral formulations of bromocriptine as bromocriptine mesilate

Drugs List

Therapeutic Indications

Uses

Acromegaly : Symptomatic relief
Hyperprolactinaemia
Infertility - female
Lactation - suppression of
Management of menstrual symptoms
Parkinson's disease
Prolactinoma

Inhibition/suppression of puerperal lactation for medical reasons (not recommended for routine suppression of lactation or relief of post partum pain and engorgement).

Treatment of hyperprolactinaemia in males and females with hypogonadism and/or galactorrhoea.

Treatment of menstrual disorders including polycystic ovary syndrome, amenorrhea and oligomenorrhoea, with or without galactorrhoea.

Drug-induced hyperprolactinaemic disorders.

Treatment of hyperprolactinaemic infertility (bromocriptine has also been used in the treatment of female infertility without hyperprolactinaemia).

Treatment of prolactinoma (specialist use only). Bromocriptine mesilate can be considered the first line treatment of macro-adenomas, and as an alternative to the surgical procedure, transphenoidal hypophysectomy, in patients with micro-adenomas.

Adjunctive treatment with surgery and/or radiotherapy to reduce circulating growth hormone in acromegaly (specialist use only).

Treatment of idiopathic Parkinson's disease either alone or in combination with levodopa.

Dosage

In most indications, the optimum response with minimal side effects is achieved by gradual introduction of bromocriptine according to the schedule below. This may be used regardless of the final dose required.

Initially take 1 mg to 1.25 mg at bedtime, increasing after 2 to 3 days to 2 mg to 2.5 mg at bedtime. The dose may then be increased by 1 mg at 2 to 3 day intervals until a dosage of 2.5 mg twice daily is achieved. If further dose increases are necessary, these should be introduced in a similar manner.

Variations to this schedule are detailed below under the specific indications (see Dosage; Adults)

Adults

Elderly

Children

Adolescents

Contraindications

Children under 7 years
Breastfeeding
Cardiac valvulopathy
Eclampsia
Galactosaemia
History of severe cardiovascular disorder
History of severe psychiatric disorder
Porphyria
Pre-eclampsia
Pregnancy-induced hypertension
Severe cardiovascular disorder
Severe psychiatric disorder
Uncontrolled hypertension

Precautions and Warnings

Children aged 7 to 17 years
History of fibrotic disorder
History of serosal inflammatory disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of peptic ulcer
Hypertension
Lactose intolerance
Pituitary neoplasm
Pregnancy
Raynaud's syndrome

Corticosteroid cover required in adrenal insufficiency
Advise patient hypotension may affect ability to drive or operate machinery
Advise patient somnolence may affect ability to drive or operate machinery
Advise patient that sudden onset sleep episodes may affect ability to drive
Consider stopping diuretic 2-3 days prior to therapy if appropriate
In pituitary tumours, treat the underlying condition
Contains lactose
Baseline assessment of inflammatory markers/ESR advised
Baseline assessment of lung function advised
Evaluate pituitary function before initiating long term therapy
Monitor visual field status before and during treatment
Perform chest X-ray prior to and periodically during treatment
Annual gynaecological assessment in women with regular menstruation
Discontinue if signs of gastro-intestinal bleeding occur
Monitor blood pressure especially at the start of treatment
Monitor for signs of pituitary tumour expansion
Monitor for signs of retroperitoneal fibrosis in Parkinsonian patients
Monitor patients for impulse control disorders
Monitor renal function especially during the initial phase of treatment
Six monthly gynaecological assessment in postmenopausal women
Advise patient to report new visual problems and symptoms
Advise patients to report signs or symptoms of gastro-intestinal ulcer
Dopamine agonists have been associated with pathological gambling
Investigate occurrence of visual disturbance or severe headache
May cause fibrotic changes
Avoid abrupt withdrawal
Advise patient to seek advice at first indications of pregnancy
Discontinue if headaches occur
Discontinue if hypertension develops
Discontinue or reduce dose if CNS toxicity occurs
Discontinue treatment if fibrotic or serosal inflammatory changes occur
If evidence of tumour expansion appears, consider alternative procedures
Reduce dose or discontinue if sudden onset of sleep during daily activities
Not licensed for all indications in all age groups
Advise patient to avoid alcohol during treatment
Female: Contraception required if pregnancy not desired
Breastfeeding: Do not breastfeed if lactation suppression fails

Hyperprolactinaemia may be idiopathic, drug-induced or due to hypothalamic or pituitary disease. The possibility of a pituitary tumour should be investigated, prior to the initiation of bromocriptine. Although bromocriptine will lower prolactin levels in patients with pituitary tumours, treatment with radiotherapy or surgery is still required for the underlying condition.

If pregnancy occurs during bromocriptine therapy for pituitary adenoma, careful monitoring is essential as prolactin-secreting adenomas may expand during pregnancy compressing the optic or other cranial nerves and necessitating emergency surgery.

Visual field impairment is a known complication of macro-prolactinoma. Effective treatment with bromocriptine should restore vision. However, some patients may experience a secondary deterioration of visual fields despite prolactin levels corrected by bromocriptine therapy. A reduction in the dose of bromocriptine may be required if secondary visual impairment occurs. It is essential to monitor visual fields in patients with macro-prolactinomas, to enable early diagnosis of visual impairment and corrective action.

Women being treated with bromocriptine for reasons other than hyperprolactinaemia should be treated with the lowest effective dose to avoid suppression of prolactin below normal levels, with subsequent impairment of luteal function.

Bromocriptine is an ergot derivative. Fibrotic and serosal inflammatory disorders such as pleuritis, pleural and pericardial effusion, pleural and pulmonary fibrosis, constrictive pericarditis, and retroperitoneal fibrosis have occurred after prolonged use of ergot derivatives. Patients with Parkinson's disease with a history of any of these conditions should not be treated with bromocriptine, unless the potential benefit outweighs the risk. The risk of fibrosis with bromocriptine is increased at high doses for long periods of time.
Attention should be paid to the signs and symptoms of;
- Pleuro-pulmonary disease such as dyspnoea, shortness of breath, persistent cough or chest pain.
- Renal insufficiency or ureteral/abdominal vascular obstruction that may occur with pain in the loins/flank and lower limb oedema, as well as any possible abdominal masses or tenderness that may indicate retroperitoneal fibrosis.
- Cardiac failure, as this can be a manifestation of constrictive pericarditis. If cardiac failure occurs, constrictive pericarditis should be excluded.

Some brands contain disodium edetate.

Pregnancy and Lactation

Pregnancy

Bromocriptine has been used throughout pregnancy and there have been a number of studies (more than 2000 pregnancies) into bromocriptine's possible effects on pregnancy. These studies reported a slight increase in the rate of early miscarriage. The incidence of congenital defects reported was 3.5%, this was considered similar to the expected rate in the general population. Long term studies on 213 children followed up to 6 years of age have shown normal mental and physical development. During pregnancy rapid expansion of pituitary tumours sometimes occurs. The manufacturers suggest that, due to the lack of evidence of a link to teratogenic effects, patients who have large tumours, or experience tumour expansion should receive bromocriptine treatment. Schaefer, Peters & Miller (2007) suggest that bromocriptine is the first line treatment for hyperprolactinaemic amenorrhoea, that bromocriptine should be discontinued after conception however continuing treatment is not grounds for termination of pregnancy or invasive diagnostic procedures. Schaefer, Peters & Miller (2007) suggest that patients, who experience ophthalmological complications in connection with macro-prolactinoma, should receive bromocriptine treatment. Overall, bromocriptine should be used with caution in pregnancy, and the mother closely monitored for side effects and avoided if possible.

Treatment with bromocriptine will result in ovulation in female patients. Patients who do not wish to conceive should be advised to use effective contraception, noting that oral contraceptives have been reported to increase serum prolactin levels.

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 14-17 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 ).

Licensed in pregnancy? - No.

Recommended for use in pregnancy? - Yes, for the treatment of large or expanding pituitary tumours and ophthalmological complications of macro-prolactinoma.

Known human teratogen? - No.

Other information - Bromocriptine treatment will result in ovulation in female patients. Patients who do not want to conceive should use effective contraception, noting that oral contraceptives have been reported to increase serum prolactin levels.

Lactation

Bromocriptine should not be used while breastfeeding. Bromocriptine suppresses lactation and therefore is contraindicated while breastfeeding. A number of reports from mothers have not reported any adverse effects. However, maternal deaths have been reported due to cerebrovascular and cardiovascular events and seizures, as a side effect of bromocriptine. Patients given bromocriptine produce milk with higher protein constituents similar to those of colostrum. Schaeffer, Peters & Miller (2007) and Hale (2006) suggest that the prolactin inhibitor cabergoline is the preferred drug for suppression of lactation in nursing mothers. Bromocriptine should not be used while breastfeeding. Patients should avoid breastfeeding for 5 days if bromocriptine has failed to suppress lactation.

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

Drug excreted in breast milk? - Unknown.

Considered suitable or recommended by the manufacturer? - No, contraindicated.

Drug substance licensed in infants? - No.

Drug known to affect lactation? - Yes, bromocriptine suppresses lactation. Milk produced by mother receiving bromocriptine has a higher than normal protein content.

Side Effects

Abdominal pain
Allergic skin reactions
Alopecia (transient)
Arrhythmias
Binge eating
Blurred vision
Bradycardia
Cardiac valvulopathy
Collapse
Confusion
Constipation
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dyskinesia
Dyspnoea
Exacerbation of Raynaud's disease
Fatigue
Gastro-intestinal ulceration and bleeding
Hallucinations
Headache
Hypersexuality
Hypertension
Hypotension
Increased libido
Insomnia
Leg cramps
Myocardial infarction
Nasal congestion
Nausea
Neuroleptic malignant syndrome-like effect
Paraesthesia
Pathological gambling
Pericardial effusion
Pericarditis
Peripheral oedema
Pleural effusion
Pleural fibrosis
Pleuritis
Postural hypotension
Psychiatric disorders
Psychomotor excitation
Psychosis
Pulmonary fibrosis
Retroperitoneal fibrosis
Seizures
Somnolence
Stroke
Sudden sleep onset episodes
Tachycardia
Tinnitus
Visual disturbances
Vomiting
Withdrawal symptoms

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 2013

Reference Sources

Summary of Product Characteristics: Bromocriptine 1mg tablets. Meda Pharmaceuticals Ltd. Revised November 2012.

Summary of Product Characteristics: Parlodel 1mg tablets. Meda Pharmaceuticals Ltd. Revised November 2012.
Summary of Product Characteristics: Parlodel 2.5mg tablets. Meda Pharmaceuticals Ltd. Revised November 2012.
Summary of Product Characteristics: Parlodel 5mg capsules. Meda Pharmaceuticals Ltd. Revised December 2012.
Summary of Product Characteristics: Parlodel 10mg capsules. Meda Pharmaceuticals Ltd. Revised December 2012.

British National Formulary, 65th Edition (March - September 2013) Pharmaceutical Press, London.

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

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.

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

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed). Record 432 - Bromocriptine
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last revised: October 2, 2012
Last accessed: April 22, 2013