Bromocriptine

Ergot alkaloids and derivatives have been associated with fibrotic valve thickening (eg, aortic, mitral, tricuspid); usually associated with long-term, chronic use.

Hypotension, including orthostatic hypotension and syncope, may occur, particularly upon initiation of therapy and dose escalation. In addition, hypertension, seizures, MI, and stroke have been reported. Severe headache or visual changes may precede events. The onset of reactions may be immediate or delayed (often may occur in the second week of therapy). Discontinue therapy and evaluate promptly if hypertension, severe, progressive, or unremitting headache (with or without visual disturbance), or evidence of CNS toxicity develops. In a scientific statement from the American Heart Association, bromocriptine has been determined to be an agent that may cause direct myocardial toxicity (magnitude: major) (AHA [Page 2016]).

May cause CNS depression, which may impair physical or mental abilities, and episodes of sudden sleep onset particularly in patients with Parkinson disease; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Consider dosage reduction or discontinuation of therapy if symptoms occur.

Visual or auditory hallucinations may occur when administered alone or concomitantly with levodopa; dose reductions or discontinuation may be necessary. Symptoms may persist for several weeks following discontinuation.

Dopamine agonists used for Parkinson disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as new or increased gambling urges, sexual urges, uncontrolled spending, or other intense urges. Dose reduction or discontinuation of therapy reverses these behaviors in some, but not all cases.

Risk for melanoma development is increased in Parkinson disease patients; drug causation or factors contributing to risk have not been established. Monitor all patients closely for melanoma and perform periodic skin examinations.

Cases of pleural and pericardial effusions, as well as pleural, pulmonary, and/or retroperitoneal fibrosis and constrictive pericarditis have been reported with prolonged and high-dose daily use. Discontinue therapy if fibrotic changes are suspected. Disease-related concerns:

Appropriate use: In the treatment of acromegaly, discontinuation is recommended if tumor expansion occurs during therapy. In patients treated with pituitary irradiation, withhold therapy for 4 to 8 weeks on a yearly basis to assess both the clinical effects of radiation on the disease process as well as the effects of bromocriptine. Digital vasospasm (cold sensitive) may occur in some patients with acromegaly; may require dosage reduction.

Use with caution in patients with cardiovascular disease (myocardial infarction; residual atrial, nodal, or ventricular arrhythmia).

Use with caution in patients with dementia; high doses may be associated with confusion and mental disturbances.

Avoid use in patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

Use with caution in patients with hepatic impairment; dosage adjustment may be necessary due to extensive hepatic metabolism.

Discontinuation of therapy in patients with macroadenomas has been associated with rapid regrowth of tumor and increased prolactin serum levels.

Use with caution in patients with peptic ulcer disease; severe gastrointestinal bleeding has been reported (some fatal).

Cerebrospinal fluid rhinorrhea has been observed in some of these patients.

Use with caution in patients with psychosis; dopamine agonists may exacerbate the disorder or diminish the effectiveness of drugs used to treat the disorder. Use in patients with severe psychotic disorder is not recommended. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Due to a difference in the formulation and resulting pharmacokinetics of Cycloset ("quick-release" tablet) compared to other formulations of bromocriptine, interchangeability with any other bromocriptine product is not recommended in the setting of type 2 diabetes mellitus management. Other warnings/precautions:

Not indicated for use in type 1 diabetes mellitus or diabetic ketoacidosis.

Dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on abrupt withdrawal or significant dosage reduction after long-term use; gradual dosage reduction is recommended when discontinuing therapy.

Monitoring and careful evaluation of visual changes during the treatment of hyperprolactinemia is recommended to differentiate between tumor shrinkage and traction on the optic chiasm; rapidly progressing visual field loss requires neurosurgical consultation.