Bromocriptine is extensively metabolised by the liver. The fate of bromocriptine primarily involves biliary excretion with renal excretion of two major metabolites accounting for only 6% of the total dose. It is not known whether these metabolites (2-bromolysergic acid and 2-bromoisolysergic acid) are pharmacologically active in humans. The elimination of the parent drug from plasma is biphasic, with a terminal half life of about 15 hours (range 8-20 hours). Multiple dosing may result in accumulation of bromocriptine to the extent that plasma levels may be almost double those observed following single doses.

Dosage and Administration
Bromocriptine tablets should always be taken with food.

Dosage of bromocriptine mesylate is expressed in terms of bromocriptine, and should be individualised.

Male hypogonadism:
Initial dosage 1.25mg 2 or 3 times a day gradually increasing to 5-10mg a day.

Prolactinomas:
1.25mg 2 or 3 times daily; this can be gradually increased as needed to suppress prolactin secretion.

Inhibition of lactation:
On day one take 1.25mg morning and night with food, increasing on day two to 2.5 mg twice daily. Therapy should be continued for 14 days to prevent rebound lactation. Treatment should be started as soon as possible after parturition or abortion.

Contraindications
hypersensitivity to ergot alkaloids
uncontrolled hypertension, hypertensive disorders of pregnancy, hypertension postpartum and in puerperium
coronary artery disease and other severe cardiovascular conditions
symptoms and/or history of serious psychiatric disorders.
Warnings and Precautions
Hypotension:
Blood pressure should be monitored periodically in all patients receiving bromocriptine. When used by women post-partum, it may induce hypotension, or more rarely hypertension, and should not be given for at least 4 hours post partum. Blood pressure must be monitored on several occasions initially, as development of hypertension may be delayed. Particular attention should be paid to patients who have used other drugs that can alter blood pressure.

Inhibition of Lactation:
Occasionally serious adverse reactions have been reported. These include seizures, strokes, myocardial infarction, hypertension and psychic disorders. Constant or progressively severe headache, which can be accompanied by visual disturbances, often precede by hours or days the occurrence of a seizure and/or stroke. Periodic monitoring of blood pressure is recommended in postpartum women receiving bromocriptine for the inhibition of lactation. Lactation inhibition therapy should not begin until the vital signs have stabilised and not before 4 hours after delivery, as bromocriptine may cause hypotension or sometimes hypertension in some patients. If hypertension, a severe progressive or unremitting headache (with or without visual disturbance), or the evidence of CNS toxicity develops, the drug therapy should be discontinues and the patient evaluated promptly.

Effect on ability to drive or operate machinery:
Patients should be warned that bromocriptine may cause dizziness and fainting during the first few days, and may impair their ability to drive a car or operate machinery.

Bromocriptine should be used with caution in patients with impaired liver, renal or severe cardiovascular dysfunction.


Adverse Reactions
Nausea is the most common side effect at the beginning of therapy with bromocriptine, but vomiting, dizziness, postural hypotension and fainting sometimes occur. Initial doses must be low, taken preferably at bedtime, and blood pressure should be monitored initially.

Gastrointestinal effects include abdominal cramps, epigastric pain, indigestion, constipation or diarrhoea. Occasionally, acromegalic patients on doses 10 to 60 mg bromocriptine have developed a peptic ulcer or gastrointestinal haemorrhage.

Temporary reduction of dose or administration with food may relieve these effects.

Additional side-effects include headache, nasal congestion or watery rhinorrhoea, dryness of mouth, and drowsiness.

Drugs which can increase prolactin levels, e.g. butyrophenones, phenothiazines, tricyclic antidepressants, reserpine, metoclopramide, methyldopa, pimozide, oestrogens and TRF, may reduce the efficacy of bromocriptine.


Concomitant use of bromocriptine and other ergot alkaloids is not recommended since the combination may cause potentially serious side effects such as myocardial infarction and hypertension.

Alcohol may decrease tolerability to bromocriptine.

Overdosage
Overdosage of bromocriptine may cause nausea, vomiting, dizziness, postural hypotension, sweating, drowsiness, and hallucinations. The management of acute intoxication is symptomatic. Metoclopramide may be indicated for the treatment of emesis or hallucinations.