bromocriptine mesylate

Pharmacologic classification: dopamine receptor agonist
Therapeutic classification: semisynthetic ergot alkaloid, dopaminergic agonist, antiparkinsonian, inhibitor of prolactin release, inhibitor of growth hormone release
Pregnancy risk category B

Available forms
Available by prescription only
Capsules: 5 mg
Tablets: 2.5 mg

Indications and dosages
 Amenorrhea and galactorrhea related to hyperprolactinemia; female infertility. Adults: 1.25 to 2.5 mg P.O. daily, increased by 2.5 mg daily at 3- to 7-day intervals as tolerated until optimal therapeutic effects are achieved. Maintenance dose is usually 5 to 7.5 mg daily (range, 2.5 to 15 mg daily). Up to 40 mg daily have been used.
 Acromegaly. Adults: Initially, 1.25 to 2.5 mg P.O. daily h.s. for 3 days. Another 1.25 to 2.5 mg may be added q 3 to 7 days until patient receives therapeutic benefit. Therapeutic dose range varies from 20 to 30 mg daily in most patients. Maximum dose shouldn’t exceed 100 mg daily. Doses of 20 to 60 mg daily have been administered as divided doses.
 Parkinson’s disease. Adults: Initially, 1.25 mg P.O. b.i.d. with meals. Dose may be increased by 2.5 mg daily q 14 to 28 days, up to 100 mg daily or until a maximal therapeutic response is achieved. Usual range is 10 to 40 mg/day. Safety in doses over 100 mg daily hasn’t been established.
 Premenstrual syndrome ◇. Adults: 2.5 to 7.5 mg P.O. b.i.d. from day 10 of menstrual cycle until onset of menstruation.
 Cushing’s syndrome ◇. Adults: 1.25 to 2.5 mg P.O. b.i.d. to q.i.d.
 Hepatic encephalopathy ◇. Adults: 1.25 mg P.O. daily, increased by 1.25 mg q 3 days until 15 mg is reached.
 Neuroleptic malignant syndrome related to neuroleptic drug therapy ◇. Adults: 2.5 to 5 mg P.O. 2 to 6 times per day.

Prolactin-inhibiting action: Reduces prolactin levels by inhibiting release of prolactin from the anterior pituitary gland, a direct action on the pituitary. It also may stimulate postsynaptic dopamine receptors in the hypothalamus to release prolactin-inhibitory factor via a complicated catecholamine pathway. Drug reduces high serum prolactin levels and restores ovulation and ovarian function in amenorrheic women and suppresses puerperal or nonpuerperal lactation in women with adequate gonadotropin levels and ovarian function. The average time for reversing amenorrhea is 6 to 8 weeks, but it may take up to 24 weeks.
Antiparkinsonian action: Activates dopaminergic receptors in the neostriatum of the CNS, which may produce antiparkinsonism activity. Dysregulation of brain serotonin activity also may occur. The precise role of bromocriptine in long-term treatment of parkinsonism syndrome needs further study of safety and efficacy.

Absorption: About 28% of dose is absorbed.
Distribution: About 90% to 96% is bound to serum albumin.
Metabolism: First-pass metabolism occurs with more than 90% of the absorbed dose. Metabolized completely in the liver, principally by hydrolysis, before excretion. The metabolites aren’t active or toxic.
Excretion: Primarily excreted in bile. Only 2.5% to 5.5% of dose is excreted in urine. Almost all (85%) of dose is excreted in feces within 5 days.

Route Onset Peak Duration
P.O. 2 hr 8 hr 24 hr

Contraindications and precautions
Contraindicated in patients hypersensitive to ergot derivatives and in those with uncontrolled hypertension or toxemia of pregnancy. Use cautiously in patients with renal or hepatic impairment and those with a history of MI and residual arrhythmias.

Drug-drug. Amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, reserpine: Increase prolactin levels. Bromocriptine dose may need to be increased.
Antihypertensives: Potentiates effects. Reduced dose prevents hypotension.
Drug-lifestyle. Alcohol use: Intolerance may result when high doses of bromocriptine are administered. Discourage alcohol use.

Adverse reactions
CNS: dizziness, headache, fatigue, mania, light-headedness, drowsiness, delusions, nervousness, insomnia, depression, seizures, CVA.
CV: hypotension, acute MI.
EENT: nasal congestion, blurred vision.
GI: nausea, vomiting, abdominal cramps, constipation, diarrhea, anorexia.
GU: urine retention, urinary frequency, renal insufficiency.
Hepatic: liver impairment.
Metabolic: hyperuricemia.
Skin: coolness and pallor of fingers and toes.

Effects on lab test results
• May increase BUN, alkaline phosphatase, uric acid, AST, ALT, and CK levels.

Overdose and treatment
Overdose may cause nausea, vomiting, and severe hypotension.
 Treatment includes emptying the stomach by aspiration and lavage, and administering I.V. fluids to treat hypotension.

Special considerations
• Patient must be examined carefully for pituitary tumor (Forbes-Albright syndrome). Use of bromocriptine doesn’t affect tumor size, although it may alleviate amenorrhea or galactorrhea.
• First-dose phenomenon occurs in 1% of patients. Sensitive patients may experience syncope for 15 to 60 minutes but can usually tolerate subsequent treatment without ill effects. Patient should begin therapy with lowest dose, taken at bedtime.
• Administer drug with meals, milk, or snacks to diminish GI distress.
• Monitor hepatic, hematopoietic, CV, and renal function in long-term use.
• Monitor blood pressure, especially during first few days of therapy.
• Monitor patient for pulmonary changes in long-term use.
• Monitor patient with acromegaly for cold-induced digital vasospasm and signs and symptoms of peptic ulcer.
• Alcohol intolerance may occur, especially with high doses of bromocriptine; advise patient to limit alcohol intake.
• As an antiparkinsonian, drug is usually given with levodopa or with levodopa-carbidopa. In treatment of Parkinson’s disease, if levodopa dose must be decreased because of adverse effects, daily bromocriptine doses may be increased gradually in 2.5-mg increments.
• Adverse reactions are more common when drug is given in large doses, as when treating parkinsonism.
Pregnant patients
• Discontinue drug if patient becomes pregnant. Recommend regular checks of the visual field if patient has underlying prolactin-secreting pituitary tumor.
Breast-feeding patients
• Because drug inhibits lactation, it shouldn’t be used in women who intend to breast-feed.
Pediatric patients
• Drug isn’t recommended for children younger than age 15.
Geriatric patients
• Use cautiously, particularly in patients receiving long-term, high-dose therapy. Perform regular physical assessment, paying particular attention to changes in pulmonary function and blood pressure.
• Safety hasn’t been established for long-term use at the doses required to treat Parkinson’s disease. Therapy should be started at the low end of the dosage range.

Patient education
• Advise patient that it may take 6 to 8 weeks or longer for menses to resume and for galactorrhea to be suppressed.
• Tell patient to take first dose where and when she can lie down because drowsiness commonly occurs after start of therapy.
• Instruct patient to report visual problems, severe nausea and vomiting, or acute headaches.
• Tell patient to take drug with meals to avoid GI upset.
• Warn patient that the CNS effects of drug may impair ability to perform tasks that require alertness and coordination.
• Instruct patient to use a nonhormonal contraceptive during treatment because of potential amenorrheic adverse effects.
• Advise patient to limit use of alcohol during treatment.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use