INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo ASPEN BROMOCRIPTINE

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

ASPEN BROMOCRIPTINE
2,5 mg compressed tablet

COMPOSITION:
Each tablet contains 2,5 mg
Bromocriptine

PHARMACOLOGICAL CLASSIFICATION:
A 21.12 Hormone inhibitors.

PHARMACOLOGICAL ACTION:
Bromocriptine, an ergot derivative, is a dopaminergic receptor stimulant. Dopamine, a neurotransmitter, has an effect on hypothalamic function, in particular it has an effect on prolactin secretion and can regulate growth hormone secretion. Bromocriptine inhibits the secretion of prolactin by the pituitary. Bromocriptine lowers elevated circulating growth hormone levels in acromegalics.

INDICATIONS:
1. Inhibition of lactation
  Prevention or suppression of puerperal lactation for medical reasons. Bromocriptine is not recommended for the routine suppression of lactation, or for the relief of symptoms of postpartum pain and engorgement, which can be adequately treated with simple analgesics and breast support.
2. Menstrual cycle disorders and female infertility associated with hyperprolactinaemia.
3. Hyperprolactinaemia in men
  Prolactin-related hypogonadism with loss of libido and impotence.
4. Prolactinomas
  Conservative treatment of prolactin-secreting pituitary micro-adenomas or macro-adenomas.
  Prior to surgery to reduce tumour size to facilitate removal or after surgery if prolactin level is still elevated.
5. Certain cases of acromegaly as adjunctive therapy
  Bromocriptine has been used in a number of specialised units, as an adjunct to surgery and/or radiotherapy, to reduce circulating growth hormone levels in the management of acromegalic patients.
6. Parkinsonism
  Idiopathic and postencephalitic Parkinson's disease, either in monotherapy or in combination with other anti-Parkinsonian medicines.
  Bromocriptine may improve tremor, rigidity, bradykinesia and the other Parkinsonian symptoms at all stages of the disease. Bromocriptine has been of benefit to patients showing severe "on-off" reactions (swing response) and other forms of deteriorating response to levodopa. Combination with levodopa may achieve increased anti-Parkinsonian effects allowing a reduction in the dosage of either compound. Bromocriptine may also be combined with anticholinergic and/or other anti-Parkinsonian drugs. Parkinson's disease may require comparatively high doses of bromocriptine.

CONTRA-INDICATIONS:
1. Hypersensitivity to bromocriptine or other ergot alkaloids.
2. Pregnancy: See side-effects and special precautions.
3. Safety and efficacy has not been established in children.
4. Bromocriptine should not be administered to a patient with a history of psychotic disorders, hepatic disease or severe angina and myocardial infarction.
5. Patients with eclampsia or uncontrolled hypertension should not receive bromocriptine. Bromocriptine should not be used in the postpartum and in the puerperal women with high blood pressure, coronary artery disease or symptoms and/or history of serious psychotic disorders.

WARNINGS:
Caution is required when bromocriptine is being given to patients with a history of psychotic disorders, severe cardiovascular disease, peptic ulcer, or gastro-intestinal bleeding.
Serious adverse events, including hypertension, myocardial infarction, seizures or stroke may occur. Psychosis with hallucinations, delusions and confusion occurs, particularly at high doses, used to treat Parkinsonism, but has also been reported with low doses. In some patients the occurrence of seizures or stroke was preceded by severe headache and/or transient visual disturbances.
In postpartum women receiving bromocriptine, blood pressure should be carefully monitored, especially during the first days of therapy. Particular caution is required in patients who have recently been treated or are on concomitant therapy with medicines that can alter blood pressure.
Hypotension may occur especially at initiation of therapy.
Although there is no conclusive evidence of an interaction between bromocriptine and other ergot alkaloids, e.g. ergometrine and methylergometrine, the concomitant use of these medications is not recommended.
If hypertension, unremitting headache, or other signs of Central Nervous System toxicity develop, treatment should be discontinued immediately.
In a few patients treated over years with bromocriptine at daily doses higher than 30 mg, retroperitoneal fibrosis has been reported. Bromocriptine medication should be withdrawn if fibrotic changes in the retroperitoneum are diagnosed or suspected.
Bromocriptine has been associated with retroperitoneal fibrosis as well as pleural thickening and effusions. Patients with unexplained pleuropulmonary disorders should be examined thoroughly and discontinuation of bromocriptine should be contemplated.
A reduction in blood pressure can occur during bromocriptine therapy, and ambulant patients should have their blood pressure checked during the first few days of treatment. Postural hypotension may be a problem and should be treated symptomatically.
Before hyperprolactinaemia with or without amenorrhoea is treated, the patient should be assessed and the possibility of a pituitary adenoma ruled out, as the tumour may progress during treatment despite clinical improvement of the patient.
Treatment of women suffering from amenorrhoea and galactorrhoea with bromocriptine will result in ovulation. If the patient does not wish to fall pregnant, appropriate contraceptive measures should be taken.
Before treatment of patients with acromegaly, patients should be assessed and only treated with bromocriptine if an alternative to conventional therapy is required. Patients treated for acromegaly have been reported to have gastro-intestinal bleeding. Acromegaly patients with a history of peptic ulceration should receive alternative treatment. If bromocriptine therapy is required, the patient must be closely observed and asked to report any gastro-intestinal side-effects immediately.
Female patients being treated for conditions not involving hyperprolactinaemia, should be given the lowest possible therapeutically effective dose to avoid suppression of prolactin below normal levels with consequent impairment of luteal function. If treatment continues for more than 6 months, post-ovulatory progesterone and plasma prolactin levels should be assessed.
Patients who drive or operate machinery should be warned of the possibility of dizziness and fainting during the first few days of treatment.
Tolerability to bromocriptine may be reduced by alcohol.

DOSAGE AND DIRECTIONS FOR USE:
Bromocriptine should always be taken with food.
1. Inhibition of lactation
a) Inhibition of normal postpartum lactation: Treatment should be administered as soon after parturition as possible, and the first tablet should be taken within the first eight hours of delivery, preferably with food. Thereafter, the patient should take one tablet, twice a day with breakfast and with the evening meal. Treatment should continue for a period of two weeks.
b) Suppression of established postpartum lactation: One tablet daily for 2 to 3 days, and thereafter one tablet, morning and night with meals for a period of two weeks. If, as sometimes happens in a small number of patients, a slight milk secretion is observed a couple of days after treatment is discontinued, treatment should be resumed or prolonged for a further week at one tablet daily.
2. Female infertility associated with hyperprolactinaemia and menstrual cycle disorders
  The patient should be instructed to take half a tablet at bedtime for three days, followed by one tablet at bedtime for a further three days. Thereafter, the patient should take one tablet twice a day with meals. If necessary, the dose may be increased to one tablet three times a day with meals. If further increases in the dosage are required, it may be increased by another tablet daily at two to three day intervals. The majority of patients should respond to a dose of 7,5 mg per day, but doses of up to 30 mg per day have been used. Treatment may have to be continued for the duration of several menstrual cycles to prevent a relapse.
3. Prolactinomas
  The usual starting dose is half a tablet two to three times daily. The dosage should be gradually increased to a maximum of 20 mg daily as may be required to control plasma prolactin levels.
4. Certain cases of acromegaly as adjunctive therapy
  Initially 1,25 mg (½ tablet) 2 or 3 times daily, gradually increasing to 10 to 20 mg daily, depending on clinical response and side-effects. Growth hormone levels must be determined from time to time to establish the correct dose of Aspen Bromocriptine.
5. Parkinson's Disease
  In order to ensure optimal tolerability, treatment should be started with a low dose of 1,25 mg (½ tablet) per day, given preferably in the evening, over the first week. Aspen Bromocriptine should be titrated slowly in order to provide each patient with the minimal effective dose. The increase in daily dosage should be gradual, by increments of 1,25 mg a day every week. The daily dosage is divided into two or three single doses. An adequate therapeutic response may be reached within 6 to 8 weeks. Otherwise, the dose may be further increased by increments of 2,5 mg a day every week. Should undesirable reactions occur during the titration phase, the daily dose is to be reduced and maintained constant for at least a week. If the adverse reactions disappear, the dose can be increased again. The usual therapeutic range for monotherapy is 10 to 40 mg bromocriptine a day. In some patients higher doses are required.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
SIDE-EFFECTS
Nausea, dizziness, vomiting and orthostatic hypotension are frequently experienced during the first few days of treatment, but should not be serious enough to warrant discontinuation of treatment.
The following side-effects have also been experienced:
Altered liver function tests, arrhythmias, cramps in the legs, headache, nasal congestion, constipation, diarrhoea, drowsiness, dry mouth, dystonia in Parkinsonism, erythromelalgia, exacerbation of angina, gastro-intestinal bleeding in acromegaly patients, headache, mental changes such as psychomotor excitation, delusions, confusion and hallucinations, micturition, mild constipation, muzziness, nasal congestion, postural hypotension, prolonged severe hypotension, reversible pallor of the fingers and toes, syncope.
Many of the side-effects are dose dependent and if they persist can be controlled by reducing the dose temporarily.
PRECAUTIONS
If the patient does wish to fall pregnant, the bromocriptine therapy should be discontinued once pregnancy has been confirmed, unless a medical reason exists for continuing therapy.
If the patient falls pregnant whilst receiving treatment for a pituitary adenoma, and the bromocriptine therapy is stopped, the patient should be observed closely throughout the pregnancy. If the patient shows symptoms of a pronounced enlargement of a prolactinoma the bromocriptine therapy can be reinstated, or surgery may be considered appropriate.
Patients receiving daily doses of bromocriptine of 20 mg or more have reported episodes of cold induced reversible pallor of the fingers and toes, especially patients who have previously exhibited Raynaud's phenomenon.
High doses of bromocriptine should only be used for the indications of acromegaly and Parkinson's.
All female patients who receive bromocriptine therapy for more than 6 months at a time should have regular gynaecological assessments, annually for pre-menopausal patients and 6 monthly for post-menopausal patients. The assessment should include cervical and endometrial cytology.
Patients receiving bromocriptine for long periods should have periodic liver function tests.

INTERACTIONS:
Bromocriptine plasma levels may be increased when erythromycin is taken concomitantly.
Dopamine antagonists such as phenothiazines, butyrophenones, thioxanthines and metoclopramide may decrease the prolactin lowering effect.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptoms reported include nausea, vomiting, dizziness, drowsiness, hypotension, sweating and hallucinations. Treatment is symptomatic and supportive.

IDENTIFICATION:
White, oval-shaped, bevelled edged tablet, slope-faced toward a score line on one side, other side flat-faced and plain.

PRESENTATION:
Available in amber glass bottles of 30 and 100 tablets.

STORAGE INSTRUCTIONS:
Store at below 25°C in a well-closed container. Protect from light and moisture.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
30/21.12/0459

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Apotex SA (Pty) Ltd,
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton
2418

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
November 1998

574953
040908        UNIPRINT-P

New addition to this site: June 2005
Source: Pharmaceutical Industry

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