Bromocriptine

Cardiovascular

Occasionally, patients taking low doses have postural hypotension, leading to dizziness or syncope. Raynaud’s syndrome, with blanching of the extremities in response to cold, is rare. At high doses some 30% suffer a peripheral cold reaction of this type, which may not become manifest for a time. Leg cramps occur in some 10% of cases. Under 10% of patients have flushing or erythromelalgia. Hypotension occurs in some 5%. Occasional cases of bradycardia or acute left ventricular failure have been described. Patients with angina pectoris can experience aggravation of their symptoms [ ]. Even acute myocardial infarction after coronary spasm has been reported [ ].

Bromocriptine has been associated with myocardial infarction, presumably because of coronary artery spasm.

• A 29-year-old woman took bromocriptine 5 mg/day postpartum to suppress lactation [ ]. Four days later she developed an acute anterior myocardial infarction. Angiography showed dissection of the left main and anterior descending arteries, with occlusion of the latter. She recovered after emergency arterial grafting.

• A 21-year-old woman had an inferior myocardial infarction, in the absence of cardiovascular risks and with normal coronary arteries on angiography [ ]. She made a good recovery, but with some persistent posterior-wall akinesia.

In another similar case the myocardial infarction proved fatal [ ].

• A 30-year-old woman collapsed and died after a first dose of bromocriptine 2.5 mg. She had severe atheroma narrowing the right coronary artery proximal to the site of thrombosis. The only obvious risk factor was heavy smoking, 30 cigarettes per day.

• A 38-year-old woman had an acute occlusion of the right popliteal artery, which gradually resolved without surgical intervention after treatment with vasodilators, anticoagulants, and antiplatelet drugs (none of which were specified) [ ]. Her serum cholesterol concentration was 8 mmol/l, but she had no other susceptibility factors.

Myocardial infarction occurred postpartum in two women taking bromocriptine [ ].

• A 33-year-old woman taking bromocriptine 5 mg/day for suppression of lactation was given ergotamine 2.25 mg for acute migraine, having taken ergotamine intermittently for over 20 years. She had a myocardial infarction involving the left anterior descending coronary artery, without apparent pre-existing atherosclerosis. She made a good recovery following thrombolysis.

• A 29-year-old woman taking bromocriptine 5 mg/day postpartum had a dissection of the left anterior descending coronary artery and needed emergency bypass grafting. She made a good recovery.

These cases emphasize the potential danger of these drugs, even in young and apparently healthy individuals, although in the first case the use of two ergot derivatives simultaneously may have been ill-advised.

Edema can occur with this and other dopamine receptor agonists, the association easily being overlooked [ ].

Fibrotic complications can extend to the heart, resulting in constrictive pericarditis.

Respiratory

Pulmonary reactions are rare. Pleural thickening and effusions and pleuropulmonary fibrosis have been observed in a few cases [ ].

Ear, nose, throat

Nasal congestion can uncommonly occur with bromocriptine [ ].

Nervous system

The high doses used in Parkinson’s disease are perhaps slightly less well tolerated than equieffective doses of levodopa.

Dyskinesias can occur with bromocriptine but less often than with equieffective doses of levodopa [ ].

Bromocriptine has been used successfully in patients with unilateral motor neglect, usually after a stroke.

• A 58-year-old man had a right middle cerebral artery infarction leading to, among many other neurological deficits, left-sided neglect [ ]. When he took bromocriptine 20 mg/day this abnormality worsened and then improved again on withdrawal.

The authors suggested that this may have been due to damage to the right putamen, while bromocriptine could still activate the striatum on the left, aggravating the hemispheric bias.

In the USA, bromocriptine has not been licensed for the suppression of lactation since 1994. Up to that time there had been no reports of intracranial hemorrhage associated with bromocriptine, but since the withdrawal of the license for this indication there have been 15 case reports of this disastrous adverse effect.

• Three women aged 22, 24, and 40 years took bromocriptine 2.5 mg bd for 2–5 days postpartum and complained of headache; two lost consciousness [ ]. One subsequently died and another had a residual neurological deficit. In all three cases intracerebral hemorrhage, confirmed by CT or MRI scans, occurred on the sixth day of administration. Maximal recorded blood pressures were 200/100, 173/120, and 180/118 mmHg.

Three cases of contractures of the extremities were possibly caused by bromocriptine [ ].

Occasionally, paresthesia and bad dreams have been described.

When the manufacturers examined reports from physicians on adverse effects from bromocriptine in inhibition of lactation, there were 38 cases of seizures [ ].

A cerebral angiopathy postpartum has also been described [ ].

Cerebrospinal fluid rhinorrhea has been described as an interesting but highly unusual sequel of bromocriptine administration [ ]. The reverse effect, air aspiration through a sellar-pharyngeal leak, has also been encountered [ ].

Sensory systems

In one series, three of 18 patients developed blurred vision during high-dose treatment of Parkinson’s disease [ ]. Diplopia has been incidentally reported. In three patients with chronic hepatic encephalopathy, reversible ototoxicity developed after the administration of bromocriptine [ ].

Psychiatric

Up to 10% of patients have to be withdrawn from treatment because of psychiatric symptoms. Bromocriptine-induced psychosis is well known and particular caution is warranted in patients with a family history of mental disorders [ ]. Even very low doses of bromocriptine can cause psychotic reactions [ ], and well-recognized problems include confusion, hallucinations, delusions, and paranoia.

Post-partum mania has been attributed to bromocriptine 5 mg/day in a 33-year-old woman after her first pregnancy [ ]. However, as the authors pointed out, the postpartum period is a high-risk period for occurrence of mood disorders and the association in this case was doubtful.

Endocrine

Inappropriate secretion of ADH has been described in a single patient [ ].

Hematologic

One case of leukopenia and thrombocytopenia has been described [ ].