- bromocriptine mesilate
POM: Prescription only medicine
This information is intended for use by health professionals
Inhibition of lactation for medical reasonsPrevention or suppression of post-partum physiological lactation only where medically indicated (such as in case of intrapartum loss, neonatal death, HIV infection of the mother).BROMOCRIPTINE is not recommended for the routine suppression of lactation or for the relief of symptoms of post-partum pain and engorgement which can be adequately treated with non-pharmacological intervention (such as firm breast support, ice application) and/or simple analgesics.
HyperprolactinaemiaThe treatment of hyperprolactinaemia in men and women with hypogonadism and/or galactorrhoea.
Menstrual cycle disorders and female infertilityAmenorrhoea and oligomenorrhoea, with or without galactorrhoea.Drug-induced hyperprolactinaemic disorders. Polycystic ovary syndrome.Some infertile women with oligomenorrhoea or amenorrhoea and galactorrhoea may be unduly sensitive to prolactin. BROMOCRIPTINE has been used successfully in the treatment of a number of infertile women with galactorrhoea who do not have demonstrable hyperprolactinaemia.
ProlactinomasTo reduce tumour size, particularly in those at risk of optic nerve compression.
AcromegalyBROMOCRIPTINE has been used in a number of specialised units, as an adjunct to surgery and/or radiotherapy to reduce circulating growth hormone in the management of acromegalic patients.
Parkinson's DiseaseIn the treatment of idiopathic Parkinson's Disease, BROMOCRIPTINE has been used both alone and in combination with Levodopa in the management of previously untreated patients and those disabled by 'on-off' phenomena. BROMOCRIPTINE has been used with occasional benefit in patients who do not respond to or are unable to tolerate Levodopa and those whose response to Levodopa is declining.Premenstrual symptoms and benign breast disease (see section 4.4 Special warnings and precautions for use).
Prevention of Lactation2.5mg on the day of delivery, followed by 2.5mg twice daily for 14 days. Treatment should be instituted within a few hours of parturition once vital signs have been stabilised. Gradual introduction of BROMOCRIPTINE is not necessary in this indication.
Suppression of Lactation for Medical Reasons2.5mg on first day, increasing after 2 to 3 days to 2.5mg twice daily for 14 days. Gradual introduction of BROMOCRIPTINE is not necessary in this indication.
Hypogonadism/Galactorrhea syndromes/InfertilityIntroduce BROMOCRIPTINE gradually according to the suggested scheme. Most patients with hyperprolactinaemia have responded to 7.5mg daily, in divided doses, but doses of up to 30mg daily have been used. In infertile patients without demonstrably elevated serum prolactin levels, the usual dose is 2.5mg twice daily.
ProlactinomasIntroduce BROMOCRIPTINE gradually according to the suggested scheme. Dosage may then be increased by 2.5mg daily at 2 to 3 day intervals, as follows:- 2.5mg eight hourly, 2.5mg six hourly, 5mg six hourly. Daily doses should not exceed 30 mg.
AcromegalyIntroduce BROMOCRIPTINE gradually, according to the suggested scheme. Dosage may then be increased by 2.5mg at 2 to 3 day intervals as follows: - 2.5mg eight-hourly, 2.5mg six-hourly, 5mg six-hourly.
Parkinson's DiseaseIntroduce BROMOCRIPTINE gradually, as follows: Week 1: 1mg to 1.25mg at bed time. Week 2: 2mg to 2.5mg at bed time. Week 3: 2.5mg twice daily. Week 4: 2.5mg three times daily. Thereafter take three times a day increasing by 2.5mg every 3 to 14 days, depending on the patient's response. Continue until the optimum dose is reached. This will usually be between 10mg and 30mg daily. Daily doses should not exceed 30 mg. In patients already receiving Levodopa the dosage of this drug may gradually be decreased, while the dosage of BROMOCRIPTINE is increased until the optimum balance is determined.
Use in Children and adolescents (aged 7-17)Prescribing of BROMOCRIPTINE in children and adolescents (aged 7-17) should be limited to Paediatric Endocrinologists.Prolactinomas: Paediatric population 7 years and older: 1 mg 2 or 3 times daily, gradually increasing to several tablets daily as required to keep plasma prolactin adequately suppressed. Maximum daily dose recommended in children aged 7 to 12 years is 5 mg. Maximum daily dose recommended in adolescent patients (13-17 years) is 20 mg. Gigantism (acromegaly): Paediatric population 7 years and older: The starting dose should be titrated in response to Growth Hormone levels. Maximum daily dose recommended in children ages 7 to 12 years is 10 mg. Maximum daily dose recommended in adolescent patients (13-17 years) is 20 mg.
Use in ElderlyThere is no clinical evidence that BROMOCRIPTINE poses a special risk to the elderly.
Use in Patients with Hepatic ImpairmentIn patients with impaired hepatic function, the speed of elimination may be retarded and plasma levels may increase, requiring dose adjustment.
OtherThere is insufficient evidence of efficacy of BROMOCRIPTINE in the treatment of premenstrual symptoms and benign breast disease. The use of BROMOCRIPTINE in patients with these conditions is therefore not recommended.In rare cases, serious adverse events, including hypertension, myocardial infarction, seizures, stroke or psychiatric disorders have been reported in postpartum women treated with BROMOCRIPTINE for inhibition of lactation. In some patients the development of seizures or stroke was preceded by severe headache and/or transient visual disturbances (see Section 4.8, Undesirable Effects). Patients with severe cardiovascular disorders or psychiatric disorders taking BROMOCRIPTINE for the indication of macro-adenomas should only take it if the perceived benefits outweigh the potential risks (see Section 4.3 Contraindications). Blood pressure should be carefully monitored, especially during the first days of therapy. Particular caution is required in patients who are on concomitant therapy with, or have recently been treated with drugs that can alter blood pressure. Concomitant use of bromocriptine with vasoconstrictors such as sympathomimetics or ergot alkaloids including ergometrine or methylergometrine during the puerperium is not recommended. If hypertension, suggestive chest pain, severe progressive or unremitting headache, or any signs of CNS toxicity develop, treatment should be discontinued immediately and the patient should be evaluated promptly. Hyperprolactinaemia may be idiopathic, drug-induced, or due to hypothalamic or pituitary disease. The possibility that hyperprolactinaemic patients may have a pituitary tumour should be recognised and complete investigation at specialised units to identify such patients is advisable. BROMOCRIPTINE will effectively lower prolactin levels in patients with pituitary tumours but does not obviate the necessity for radiotherapy or surgical intervention where appropriate in acromegaly.Since patients with macro-adenomas of the pituitary might have accompanying hypopituitarism due to compression or destruction of pituitary tissue, one should make a complete evaluation of pituitary functions and institute appropriate substitution therapy prior to administration of BROMOCRIPTINE. In patients with secondary adrenal insufficiency, substitution with corticosteroids is essential. The evolution of tumour size in patients with pituitary macro-adenomas should be carefully monitored and if evidence of tumour expansion develops, surgical procedures must be considered.If in adenoma patients, pregnancy occurs after the administration of BROMOCRIPTINE, careful observation is mandatory. Prolactin-secreting adenomas may expand during pregnancy. In these patients, treatment with BROMOCRIPTINE often results in tumour shrinkage and rapid improvement of the visual fields defects. In severe cases, compression of the optic or other cranial nerves may necessitate emergency pituitary surgery.Visual field impairment is a known complication of macroprolactinoma. Effective treatment with BROMOCRIPTINE leads to a reduction in hyperprolactinaemia and often to resolution of the visual impairment. In some patients, however, a secondary deterioration of visual fields may subsequently develop despite normalised prolactin levels and tumour shrinkage, which may result from traction on the optic chiasm which is pulled down into the now partially empty sella. In these cases the visual field defect may improve on reduction of bromocriptine dosage while there is some elevation of prolactin and some tumour re-expansion. Monitoring of visual fields in patients with macroprolactinoma is therefore recommended for an early recognition of secondary field loss due to chiasmal herniation and adaptation of drug dosage.In some patients with prolactin-secreting adenomas treated with BROMOCRIPTINE, cerebrospinal fluid rhinorrhea has been observed. The data available suggest that this may result from shrinkage of invasive tumours.Bromocriptine has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with bromocriptine. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines (see Section 4.7 Effects on ability to drive and use machines). Furthermore, a reduction of dosage or termination of therapy may be considered.When women of child-bearing age are treated with BROMOCRIPTINE for conditions not associated with hyperprolactinaemia the lowest effective dose should be used. This is in order to avoid suppression of prolactin to below normal levels, with consequent impairment of luteal function.Gynaecological assessment, preferably including cervical and endometrial cytology, is recommended for women receiving BROMOCRIPTINE for extensive periods. Six monthly assessment is suggested for post-menopausal women and annual assessment for women with regular menstruation.A few cases of gastrointestinal bleeding and gastric ulcer have been reported. If this occurs, BROMOCRIPTINE should be withdrawn. Patients with a history of evidence of peptic ulceration should be closely monitored when receiving the treatment.Since, especially during the first few days of treatment, hypotensive reactions may occasionally occur and result in reduced alertness, particular care should be exercised when driving a vehicle or operating machinery.Among patients on BROMOCRIPTINE, particularly on long-term and high-dose treatment, pleural and pericardial effusions, as well as pleural and pulmonary fibrosis and constrictive pericarditis have occasionally been reported. Patients with unexplained pleuropulmonary disorders should be examined thoroughly and discontinuation of BROMOCRIPTINE therapy should be contemplated.In a few patients on BROMOCRIPTINE, particularly on long-term and high-dose treatment, retroperitoneal fibrosis has been reported. To ensure recognition of retroperitoneal fibrosis at an early reversible stage it is recommended that its manifestations (e.g. back pain, oedema of the lower limbs, impaired kidney function) should be watched in this category of patients. BROMOCRIPTINE medication should be withdrawn if fibrotic changes in the retroperitoneum are diagnosed or suspected.Attention should be paid to the signs and symptoms of pleuro-pulmonary disease such as dyspnoea, shortness of breath, persistent cough or chest pain cardiac failure as cases of pericardial fibrosis have often manifested as cardiac failure. Constrictive pericarditis should be excluded if such symptoms appear.Appropriate investigations such as erythrocyte sedimentation rate, chest X-ray and serum creatinine measurements should be performed if necessary to support a diagnosis of a fibrotic disorder. It is also appropriate to perform baseline investigations of erythrocyte sedimentation rate or other inflammatory markers, lung function/chest X-ray and renal function prior to initiation of therapy.These disorders can have an insidious onset and patients should be regularly and carefully monitored while taking BROMOCRIPTINE for manifestations of progressive fibrotic disorders. BROMOCRIPTINE should be withdrawn if fibrotic or serosal inflammatory changes are diagnosed or suspected.Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Impulse control disordersPatients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists, including BROMOCRIPTINE. Dose reduction/tapered discontinuation should be considered if such symptoms develop.
Children and Adolescents (aged 7-17)Bromocriptine has been used to treat prolactinomas and gigantism (acromegaly) indications in patients aged 7 or above and case series have been documented in the literature. Only isolated data are available for bromocriptine use in paediatric patients under the age of 7 years. Data on safety are limited, particularly in the long term. Prescribing is restricted to Paediatric Endocrinologists.
ElderlyClinical studies for BROMOCRIPTINE did not include sufficient numbers of subjects ages 65 and above to determine whether the elderly respond differently from younger subjects. However, other reported clinical experiences, including post-marketing reporting of adverse events have identified no differences in response or tolerability between elderly and younger patients.Even though no variation in efficacy or adverse reaction profile in elderly patients taking BROMOCRIPTINE has been observed, greater sensitivity in some elderly individuals cannot be categorically ruled out. In general, dose selection for an elderly patient should be cautious, starting at the lower end of the dose range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy in this population.
PregnancyIf pregnancy occurs it is generally advisable to withdraw BROMOCRIPTINE after the first missed menstrual period.Rapid expansion of pituitary tumours sometimes occurs during pregnancy and this may also occur in patients who have been able to conceive as a result of BROMOCRIPTINE therapy. As a precautionary measure, patients should be monitored to detect signs of pituitary enlargement so that BROMOCRIPTINE may be reintroduced if necessary. Based on the outcome of more than 2,000 pregnancies, the use of BROMOCRIPTINE to restore fertility has not been associated with an increased risk of abortion, premature delivery, multiple pregnancy or malformation in infants. Because this accumulated evidence suggests a lack of teratogenic or embryopathic effects in humans, maintenance of BROMOCRIPTINE treatment during pregnancy may be considered where there is a large tumour or evidence of expansion.
LactationSince BROMOCRIPTINE inhibits lactation, it should not be administered to mothers who elect to breast-feed.
Women of child-bearing potentialFertility may be restored by treatment with BROMOCRIPTINE. Women of childbearing age who do not wish to conceive should therefore be advised to practice a reliable method of contraception.
Nervous System DisordersCommon: Headache, Drowsiness, Uncommon: Dizziness, DyskinesiaRare: Somnolence, ParaesthesiaVery Rare: Excess daytime somnolence and sudden sleep onset
Psychiatric DisordersUncommon: Confusion, Psychomotor agitation, Hallucinations Rare: Psychotic disorders, Insomnia
Gastrointestinal DisordersCommon: Nausea, Constipation Uncommon: Vomiting Uncommon: Dry mouth Rare: Diarrhoea, Abdominal pain, Retroperitoneal fibrosis, Gastrointestinal ulcer, Gastrointestinal haemorrhage
Vascular DisordersUncommon: Hypotension including orthostatic hypotension (which may in very rare instances lead to collapse) Very Rare: Reversible pallor of fingers and toes induced by cold (especially in patients who have a history of Raynaud's phenomenon)
Cardiac DisordersRare: Tachycardia, bradycardia, arrhthymiaVery rare: Cardiac valvulopathy (including regurgitation) and related disorders (pericarditis and pericardial effusion).
Respiratory, thoracic and mediastinal disordersCommon: Nasal congestion Rare: Pleural effusion, pleural and pulmonary fibrosis, pleuritis, dyspneoa
Musculoskeletal and connective tissue disordersUncommon: Leg cramps
Skin and subcutaneous tissue disordersUncommon: Allergic skin reactions, Hair loss
General disorders and administration site conditionsUncommon: FatigueRare: Peripheral oedemaVery Rarely: A syndrome resembling Neuroleptic Malignant Syndrome has been reported on withdrawal of BROMOCRIPTINE.
Eye DisordersRare: Visual disturbances, vision blurred
Ear and Labyrinth DisordersRare: Tinnitus
Post-partum womenIn extremely rare cases (in postpartum women treated with BROMOCRIPTINE for the prevention of lactation) serious adverse events including hypertension, myocardial infarction, convulsion, stroke or mental disorders have been reported, although the causal relationship is uncertain. In some patients the occurrence of convulsion or stroke was preceded by severe headache and/or transient visual disturbances (see Section 4.4 Special warnings and precautions for use).
Impulse control disordersPathological gambling, increased libido hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including BROMOCRIPTINE. (see section 4.4 'Special warnings and precautions for use'). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
Signs and SymptomsOverdosage with BROMOCRIPTINE is likely to result in vomiting and other symptoms which could be due to over stimulation of dopaminergic receptors and might include nausea, dizziness, hypotension, postural hypotension, tachycardia, drowsiness, somnolence, lethargy, confusion and hallucinations. General supportive measures should be undertaken to remove any unabsorbed material and maintain blood pressure if necessary.There have been isolated reports of children who accidentally ingested BROMOCRIPTINE. Vomiting, somnolence and fever were reported as adverse events. Patients recovered either spontaneously within a few hours or after symptomatic treatment.
Overdose managementIn the case of overdose, administration of activated charcoal is recommended and in the case of very recent oral intake, gastric lavage may be considered.The management of acute intoxication is symptomatic; Metoclopramide may be indicated for the treatment of emesis or hallucinations.
Endocrinological indicationsBROMOCRIPTINE inhibits the secretion of the anterior pituitary hormone prolactin without affecting normal levels of other pituitary hormones. However, BROMOCRIPTINE is capable of reducing elevated levels of growth hormone (GH) in patients with acromegaly. These effects are due to stimulation of dopamine receptors.In the puerperium prolactin is necessary for the initiation and maintenance of puerperal lactation. At other times increased prolactin secretion gives rise to pathological lactation (galactorrhoea) and/or disorders of ovulation and menstruation.As a specific inhibitor of prolactin secretion, BROMOCRIPTINE can be used to prevent or suppress physiological lactation as well as to treat prolactin-induced pathological states. In amenorrhoea and/or anovulation (with or without galactorrhoea), BROMOCRIPTINE can be used to restore menstrual cycles and ovulation.The customary measures taken during lactation suppression, such as the restriction of fluid intake are not necessary with BROMOCRIPTINE. In addition, BROMOCRIPTINE does not impair the puerperal involution of the uterus and does not increase the risk of thromboembolism.BROMOCRIPTINE has been shown to arrest the growth or to reduce the size of prolactin-secreting pituitary adenomas (prolactinomas).In acromegalic patients - apart from lowering the plasma levels of growth hormone and prolactin - BROMOCRIPTINE has a beneficial effect on clinical symptoms and on glucose tolerance.BROMOCRIPTINE improves the clinical symptoms of the polycystic ovary syndrome by restoring a normal pattern of LH secretion.
Neurological IndicationsBecause of its dopaminergic activity, BROMOCRIPTINE, in doses usually higher than those for endocrinological indications, is effective in the treatment of Parkinson's Disease, which is characterised by a specific nigrostriatal dopamine deficiency. The stimulation of dopamine receptors by BROMOCRIPTINE can in this condition restore the neurochemical balance within the striatum.Clinically, BROMOCRIPTINE improves tremor, rigidity, bradykinesia and other Parkinsonian symptoms at all stages of the disease. Usually the therapeutic effect lasts over years (so far, good results have been reported in patients treated up to eight years). BROMOCRIPTINE can be given either alone or - at early as well as advanced stages - combined with other anti-Parkinsonian drugs. Combination with Levodopa treatment results in enhanced anti-Parkinsonian effects, often making possible a reduction of the Levodopa dose. BROMOCRIPTINE offers particular benefit to patients on Levodopa treatment exhibiting a deteriorating therapeutic response or complications such as abnormal involuntary movements (choreoatoid dykinesia and/or painful dystonia), end-of-dose failure, and 'on-off' phenomenon.BROMOCRIPTINE improves the depressive symptomatology often observed in Parkinsonian patients. This is due to its inherent antidepressant properties as substantiated by controlled studies in non-Parkinsonian patients with endogenous or psychogenic depression.
BiotransformationBromocriptine undergoes extensive first-pass biotransformation in the liver, reflected by complex metabolite profiles and by almost complete absence of parent drug in urine and faeces. It shows a high affinity for CYP3A and hydroxylations at the proline ring of the cyclopeptide moiety constitute a main metabolic pathway. Inhibitors and/or potent substrates for CYP3A4 might therefore be expected to inhibit the clearance of bromocriptine and lead to increased levels. Bromocriptine is also a potent inhibitor of CYP3A4 with a calculated IC50 value of 1.69 µM. However, given the low therapeutic concentrations of free bromocriptine in patients, a significant alteration of the metabolism of a second drug whose clearance is mediated by CYP3A4 should not be expected.
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