BRAMESTON Tablet Ref.[28179] Active ingredients: Bromocriptine

If women with conditions not associated with hyperprolactinaemia are treated with Brameston, the drug should be given in the lowest effective dose necessary to relieve the symptoms; this is in order to avoid the possibility of suppressing plasma prolactin below normal levels, with a consequent impairment of luteal function.

A few cases of gastrointestinal bleeding and gastric ulcer have been reported. If this occurs, Brameston should be withdrawn. Patients with a history or evidence of peptic ulceration should be closely monitored when receiving the treatment.

Since, especially during the first 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.

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 not to drive or operate machines during treatment with bromocriptine.

Patients who have experienced somnolence and/or an episode of sudden sleep onset must not drive or operate machines. Furthermore, a reduction of dosage or termination of therapy may be considered.

Patients 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 Brameston; dose reduction/tapered discontinuation should be considered if such symptoms develop.

Use in postpartum women

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. Blood pressure should be carefully monitored, especially during the first days of therapy. If hypertension, severe, progressive, or unremitting headache (with or without visual disturbances), or evidence of CNS toxicity develop, the administration of Brameston should be discontinued and the patient should be evaluated promptly.

Particular caution is required in patients who have recently been treated or are on concomitant therapy drugs that can alter blood pressure e.g. vasoconstrictors such as sympathomimetics or ergot alkaloids including ergometrine or methylergometrine during the puerperium is not recommended.

Use in prolactin-secreting adenoma patients

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 Brameston. 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 Brameston, 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 Brameston 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 Brameston, cerebrospinal fluid rhinorrhea has been observed. The data available suggest that this may result from shrinkage of invasive tumours.

Use in Parkinsonian patients

Among patients on bromocriptine 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

Brameston therapy should be contemplated.

In a few patients treated 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. Brameston medication should be withdrawn if fibrotic changes in the retroperitoneum are diagnosed or suspected.

Children and Adolescents (aged 7 to 17)

The safety and effectiveness of bromocriptine in paediatric patients has only been established for the Prolactinomas and Acromegaly indications, in patients aged 7 or above. Only isolated data are available for bromocriptine use in paediatric patients under the age of 7 years. However, other reported clinical experiences, including post-marketing reporting of adverse events, have not identified differences in tolerability between adults and adolescents or children.

Even though no variation in adverse reaction profile in paediatric patients taking bromocriptine has been observed, greater sensitivity in some younger individuals cannot be categorically ruled out, and it is recommended that dose titration in paediatric patients should be cautious.

Older people

Clinical studies for bromocriptine did not include sufficient numbers of subjects aged 65 and above to determine whether older people 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 older people and younger patients.

Even though no variation in efficacy or adverse reaction profile in older people patients taking bromocriptine has been observed, greater sensitivity in some older individuals cannot be categorically ruled out. In general, dose selection for an older 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.

Brameston contains lactose

Patients with rare hereditary problems of galactose intolerance, the severe lactase deficiency of glucose-galactose malabsorption should not take this medicine.

Bromocriptine is both a substrate and an inhibitor of CYP3A4 (see Section 5.2 Pharmacokinetic properties). Caution should therefore be used when co-administering drugs which are strong inhibitors and/or substrates of this enzyme (azole antimycotics, HIV protease inhibitors). The concomitant treatment of acromegalic patients with bromocriptine and octreotide led to increased plasma levels of bromocriptine. The concomitant treatment of acromegalic patients with bromocriptine and octreotide led to increased plasma levels of bromocriptine.

Since bromocriptine exerts its therapeutic effect by stimulating central dopamine receptors, dopamine antagonists such as antipsychotics (phenothiazines, butyrophenones and thioxanthenes), but also metoclopramide and domperidone may reduce its activity.

The tolerability to Brameston may be reduced by alcohol.

Pregnancy

In patients wishing to conceive, Brameston, like all other drugs, should be discontinued when pregnancy is confirmed, unless there is a medical reason for continuing therapy. No increased incidence of abortion has been observed following withdrawal of bromocriptine at this point. Clinical experience indicated that bromocriptine, administered during pregnancy, does not adversely affect its course or outcome.

If pregnancy occurs in the presence of a pituitary adenoma and Brameston treatment has been stopped, close supervision throughout pregnancy is essential. In patients who show symptoms of a pronounced enlargement of a prolactinoma, e.g. headache or visual field deterioration, Brameston treatment may be re-instituted or surgery may be appropriate.

Breast-feeding

Since bromocriptine inhibits lactation it should not be given to mothers planning to breast-feed.

Fertility

Fertility may be restored by treatment with Brameston. Women of childbearing age who do not wish to conceive should therefore be advised to practice a reliable method of contraception.

Since, especially during the first days of treatment, hypotensive reactions may occasionally occur and result in reduced alertness particular care should be exercised when driving vehicles or operating machinery.

Patients being treated with bromocriptine and presenting with somnolence and/or sudden sleep episodes must be advised not to drive or engage in activities where impaired alertness may put themselves or others at risk of serious injury or death (eg. operating machines) until such recurrent episodes and somnolence have resolved (see 4.4 Special warnings and precautions for use).

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (1/10); common (1/100, <1/10); uncommon (1/1,000, <1/100); rare (1/10,000, <1/1,000), very rare (<1/10,000), including isolated reports.

Table 1:

The use of bromocriptine for the inhibition of physiological lactation post-partum has been associated with the rare occurrence of hypertension, myocardial infarction, seizures, stroke or psychic disorders (see section 4.4 Special warnings and precautions for use).

Impulse control disorders

Pathological 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 continue monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: Cyprus, Pharmaceutical Services, Ministry of Health, CY-1475 Nicosia, Fax: +357 22608649, Website: www.moh.gov.cy/phs.

Not applicable.