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Bromocriptine

Pronunciation

Generic Name: Bromocriptine mesylate
Dosage Form: tablet

Bromocriptine Description

Bromocriptine mesylate is an ergot derivative with potent dopamine receptor agonist activity. Each Bromocriptine mesylate tablet for oral administration contains 2.5 mg and each capsule contains 5 mg Bromocriptine (as the mesylate). Bromocriptine mesylate is chemically designated as Ergotaman‑3′,6′,18‑trione, 2‑bromo‑12′‑hydroxy‑2′‑ (1‑methylethyl)‑5′‑(2‑methylpropyl)‑, (5′α)‑monomethanesulfonate (salt).

The structural formula is:

2.5 mg Tablets

Active Ingredient:  Bromocriptine mesylate, USP

Inactive Ingredients: colloidal silicon dioxide, lactose, magnesium stearate, maleic acid, povidone, starch, and another ingredient

5 mg Capsules

Active Ingredient:  Bromocriptine mesylate, USP

Inactive Ingredients: colloidal silicon dioxide, gelatin, lactose, magnesium stearate, red iron oxide, silicon dioxide, sodium lauryl sulfate, starch, maleic acid, titanium dioxide, yellow iron oxide, and another ingredient.

Bromocriptine - Clinical Pharmacology

Bromocriptine mesylate is a dopamine receptor agonist, which activates post-synaptic dopamine receptors. The dopaminergic neurons in the tuberoinfundibular process modulate the secretion of prolactin from the anterior pituitary by secreting a prolactin inhibitory factor (thought to be dopamine); in the corpus striatum the dopaminergic neurons are involved in the control of motor function. Clinically, Bromocriptine significantly reduces plasma levels of prolactin in patients with physiologically elevated prolactin as well as in patients with hyperprolactinemia. The inhibition of physiological lactation as well as galactorrhea in pathological hyperprolactinemic states is obtained at dose levels that do not affect secretion of other tropic hormones from the anterior pituitary. Experiments have demonstrated that Bromocriptine induces long-lasting stereotyped behavior in rodents and turning behavior in rats having unilateral lesions in the substantia nigra. These actions, characteristic of those produced by dopamine, are inhibited by dopamine antagonists and suggest a direct action of Bromocriptine on striatal dopamine receptors.

Bromocriptine mesylate is a nonhormonal, nonestrogenic agent that inhibits the secretion of prolactin in humans, with little or no effect on other pituitary hormones, except in patients with acromegaly, where it lowers elevated blood levels of growth hormone in the majority of patients.

Bromocriptine mesylate produces its therapeutic effect in the treatment of Parkinson's disease, a clinical condition characterized by a progressive deficiency in dopamine synthesis in the substantia nigra, by directly stimulating the dopamine receptors in the corpus striatum. In contrast, levodopa exerts its therapeutic effect only after conversion to dopamine by the neurons of the substantia nigra, which are known to be numerically diminished in this patient population.

Pharmacokinetics

Clinical Studies

In about 75% of cases of amenorrhea and galactorrhea, Bromocriptine therapy suppresses the galactorrhea completely, or almost completely, and reinitiates normal ovulatory menstrual cycles.

Menses are usually reinitiated prior to complete suppression of galactorrhea; the time for this on average is 6-8 weeks. However, some patients respond within a few days, and others may take up to 8 months.

Galactorrhea may take longer to control depending on the degree of stimulation of the mammary tissue prior to therapy. At least a 75% reduction in secretion is usually observed after 8-12 weeks. Some patients may fail to respond even after 12 months of therapy.

In many acromegalic patients, Bromocriptine produces a prompt and sustained reduction in circulating levels of serum growth hormone.

Indications and Usage for Bromocriptine

Hyperprolactinemia-Associated Dysfunctions

Bromocriptine mesylate is indicated for the treatment of dysfunctions associated with hyperprolactinemia including amenorrhea with or without galactorrhea, infertility or hypogonadism. Bromocriptine treatment is indicated in patients with prolactin-secreting adenomas, which may be the basic underlying endocrinopathy contributing to the above clinical presentations. Reduction in tumor size has been demonstrated in both male and female patients with macroadenomas. In cases where adenectomy is elected, a course of Bromocriptine therapy may be used to reduce the tumor mass prior to surgery.

Acromegaly

Bromocriptine therapy is indicated in the treatment of acromegaly. Bromocriptine therapy, alone or as adjunctive therapy with pituitary irradiation or surgery, reduces serum growth hormone by 50% or more in approximately half of patients treated, although not usually to normal levels.

Since the effects of external pituitary radiation may not become maximal for several years, adjunctive therapy with Bromocriptine offers potential benefit before the effects of irradiation are manifested.

Parkinson's Disease

Bromocriptine mesylate tablets or capsules are indicated in the treatment of the signs and symptoms of idiopathic or postencephalitic Parkinson's disease. As adjunctive treatment to levodopa (alone or with a peripheral decarboxylase inhibitor), Bromocriptine therapy may provide additional therapeutic benefits in those patients who are currently maintained on optimal dosages of levodopa, those who are beginning to deteriorate (develop tolerance) to levodopa therapy, and those who are experiencing "end of dose failure'' on levodopa therapy. Bromocriptine therapy may permit a reduction of the maintenance dose of levodopa and, thus may ameliorate the occurrence and/or severity of adverse reactions associated with long-term levodopa therapy such as abnormal involuntary movements (e.g., dyskinesias) and the marked swings in motor function ("on-off'' phenomenon). Continued efficacy of Bromocriptine therapy during treatment of more than 2 years has not been established.

Data are insufficient to evaluate potential benefit from treating newly diagnosed Parkinson's disease with Bromocriptine. Studies have shown, however, significantly more adverse reactions (notably nausea, hallucinations, confusion and hypotension) in Bromocriptine-treated patients than in levodopa/carbidopa-treated patients. Patients unresponsive to levodopa are poor candidates for Bromocriptine therapy.

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Contraindications

Hypersensitivity to Bromocriptine or to any of the excipients of Bromocriptine mesylate, uncontrolled hypertension and sensitivity to any ergot alkaloids. In patients being treated for hyperprolactinemia, Bromocriptine should be withdrawn when pregnancy is diagnosed (see PRECAUTIONS, Hyperprolactinemic States). In the event that Bromocriptine is reinstituted to control a rapidly expanding macroadenoma (see PRECAUTIONS, Hyperprolactinemic States) and a patient experiences a hypertensive disorder of pregnancy, the benefit of continuing Bromocriptine must be weighed against the possible risk of its use during a hypertensive disorder of pregnancy. When Bromocriptine is being used to treat acromegaly, prolactinoma, or Parkinson's disease in patients who subsequently become pregnant, a decision should be made as to whether the therapy continues to be medically necessary or can be withdrawn. If it is continued, the drug should be withdrawn in those who may experience hypertensive disorders of pregnancy (including eclampsia, preeclampsia, or pregnancy-induced hypertension) unless withdrawal of Bromocriptine is considered to be medically contraindicated.

The drug should not be used during the postpartum period in women with a history of coronary artery disease and other severe cardiovascular conditions unless withdrawal is considered medically contraindicated. If the drug is used in the postpartum period, the patient should be observed with caution.

Warnings

Since hyperprolactinemia with amenorrhea/galactorrhea and infertility has been found in patients with pituitary tumors, a complete evaluation of the pituitary is indicated before treatment with Bromocriptine mesylate.

If pregnancy occurs during Bromocriptine administration, careful observation of these patients is mandatory. Prolactin-secreting adenomas may expand and compression of the optic or other cranial nerves may occur, emergency pituitary surgery becoming necessary. In most cases, the compression resolves following delivery. Reinitiation of Bromocriptine treatment has been reported to produce improvement in the visual fields of patients in whom nerve compression has occurred during pregnancy. The safety of Bromocriptine treatment during pregnancy to the mother and fetus has not been established.

Bromocriptine has been associated with somnolence, and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported. Patients must be informed of this and advised not to drive or operate machines during treatment with Bromocriptine. Patients who have experienced somnolence and/or an episode of sudden sleep onset must not drive or operate machines. Furthermore, a reduction of dosage or termination of therapy may be considered.

Symptomatic hypotension can occur in patients treated with Bromocriptine for any indication. In postpartum studies with Bromocriptine, decreases in supine systolic and diastolic pressures of greater than 20 mm and 10 mm Hg, respectively, have been observed in almost 30% of patients receiving Bromocriptine. On occasion, the drop in supine systolic pressure was as much as 50-59 mm of Hg.

Since, especially during the first days of treatment, hypotensive reactions may occasionally occur and result in reduced alertness, particular care should be exercised when driving a vehicle or operating machinery.

While hypotension during the start of therapy with Bromocriptine occurs in some patients, in rare cases serious adverse events, including hypertension, myocardial infarction, seizures, stroke, have been reported in postpartum women treated with Bromocriptine for the inhibition of lactation. Hypertension have been reported, sometimes at the initiation of therapy, but often developing in the second week of therapy; seizures have also been reported both with and without the prior development of hypertension; stroke have been reported mostly in postpartum patients whose prenatal and obstetric courses had been uncomplicated. Many of these patients experiencing seizures (including cases of status epilepticus) and/or strokes reported developing a constant and often progressively severe headache hours to days prior to the acute event. Some cases of strokes and seizures were also preceded by visual disturbances (blurred vision, and transient cortical blindness). Cases of acute myocardial infarction have also been reported.

Although a causal relationship between Bromocriptine administration and hypertension, seizures, strokes, and myocardial infarction in postpartum women has not been established, use of the drug for prevention of physiological lactation, or in patients with uncontrolled hypertension is not recommended. In patients being treated for hyperprolactinemia, Bromocriptine should be withdrawn when pregnancy is diagnosed (see PRECAUTIONS, Hyperprolactinemic States). In the event that Bromocriptine is reinstituted to control a rapidly expanding macroadenoma (see PRECAUTIONS, Hyperprolactinemic States) and a patient experiences a hypertensive disorder of pregnancy, the benefit of continuing Bromocriptine must be weighed against the possible risk of its use during a hypertensive disorder of pregnancy. When Bromocriptine is being used to treat acromegaly or Parkinson's disease in patients who subsequently become pregnant, a decision should be made as to whether the therapy continues to be medically necessary or can be withdrawn. If it is continued, the drug should be withdrawn in those who may experience hypertensive disorders of pregnancy (including eclampsia, preeclampsia, or pregnancy-induced hypertension) unless withdrawal of Bromocriptine is considered to be medically contraindicated. Because of the possibility of an interaction between Bromocriptine and other ergot alkaloids, the concomitant use of these medications is not recommended. Periodic monitoring of the blood pressure, particularly during the first weeks of therapy is prudent. If hypertension, severe, progressive, or unremitting headache (with or without visual disturbance), or evidence of CNS toxicity develops, drug therapy should be discontinued and the patient should be evaluated promptly. Particular attention should be paid to patients who have recently been treated or are on concomitant therapy with drugs that can alter blood pressure. Their concomitant use in the puerperium is not recommended.

Among patients on Bromocriptine, particularly on long-term and high-dose treatment, pleural and pericardial effusions, as well as pleural and pulmonary fibrosis and constrictive pericarditis, have been reported. Patients with unexplained pleuropulmonary disorders should be examined thoroughly and discontinuation of Bromocriptine therapy should be considered. In those instances in which Bromocriptine treatment was terminated, the changes slowly reverted towards normal.

In a few patients on Bromocriptine, particularly on long-term and high-dose treatment, retroperitoneal fibrosis has been reported. To ensure recognition of retroperitoneal fibrosis at an early reversible stage it is recommended that its manifestations (e.g., back pain, edema of the lower limbs, impaired kidney function) should be watched in this category of patients. Bromocriptine medication should be withdrawn if fibrotic changes in the retroperitoneum are diagnosed or suspected.

Precautions

Adverse Reactions

Overdosage

The most commonly reported signs and symptoms associated with acute Bromocriptine mesylate overdose are: nausea, vomiting, constipation, diaphoresis, dizziness, pallor, severe hypotension, malaise, confusion, lethargy, drowsiness, delusions, hallucinations, and repetitive yawning. The lethal dose has not been established and the drug has a very wide margin of safety. However, one death occurred in a patient who committed suicide with an unknown quantity of Bromocriptine and chloroquine.

Treatment of overdose consists of removal of the drug by emesis (if conscious), gastric lavage, activated charcoal, or saline catharsis. Careful supervision and recording of fluid intake and output is essential. Hypotension should be treated by placing the patient in the Trendelenburg position and administering I.V. fluids. If satisfactory relief of hypotension cannot be achieved by using the above measures to their fullest extent, vasopressors should be considered.

There have been isolated reports of children who accidentally ingested Bromocriptine. Vomiting, somnolence and fever were reported as adverse events. Patients recovered either spontaneously within a few hours or after appropriate management.

Bromocriptine Dosage and Administration

How is Bromocriptine Supplied

Bromocriptine mesylate Tablets

2.5 mg

Bromocriptine mesylate tablets are available in bottles containing 30 and 100 tablets of 2.5 mg - each bottle contains a desiccant.

Round, off-white, bevelled-edge scored tablets, each containing 2.5 mg Bromocriptine (as the mesylate). Engraved “PARLODEL 2½’’ on one side and 017 twice on the scored side. Complies with USP dissolution test 1.

Packages of 30.....................................................................................NDC 63304-962-30

Packages of 100...................................................................................NDC 63304-962-01

Bromocriptine mesylate Capsules

5 mg

Caramel and white capsules, each containing 5 mg Bromocriptine (as the mesylate). Imprinted in red ink “PARLODEL 5 mg’’ on one half and 102 on other half.

Packages of 30..............................................................NDC 63304-158-30

Packages of 100............................................................NDC 63304-158-01

Store and Dispense

Below 25ºC (77ºF); tight, light-resistant container.

Distributed by:

Ranbaxy Pharmaceuticals Inc. Jacksonville, FL 32257 USA

Principal Display Panel

PRINCIPAL DISPLAY PANEL - 2.5 mg Tablets

NDC 63304-962-01

Bromocriptine mesylate Tablets, USP

Principal Display Panel

PRINCIPAL DISPLAY PANEL - 5 mg Capsules

NDC 63304-158-01

Bromocriptine mesylate Capsules, USP

Bromocriptine MESYLATE 
Bromocriptine mesylate tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:63304-962
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Bromocriptine MESYLATE (Bromocriptine) Bromocriptine 2.5 mg
Inactive Ingredients
Ingredient Name Strength
POVIDONES  
STARCH, CORN  
LACTOSE, UNSPECIFIED FORM  
MAGNESIUM STEARATE  
MALEIC ACID  
ISOPROPYL ALCOHOL  
SILICON DIOXIDE  
Product Characteristics
Color WHITE Score 2 pieces
Shape ROUND Size 8mm
Flavor Imprint Code PARLODEL;2;1;2;017
Contains     
Packaging
# Item Code Package Description
1 NDC:63304-962-01 100 TABLET in 1 BOTTLE
2 NDC:63304-962-30 30 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA017962 12/22/2016
Bromocriptine MESYLATE 
Bromocriptine mesylate capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:63304-158
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Bromocriptine MESYLATE (Bromocriptine) Bromocriptine 5 mg
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE  
POVIDONES  
STARCH, CORN  
LACTOSE, UNSPECIFIED FORM  
MAGNESIUM STEARATE  
GELATIN  
SODIUM LAURYL SULFATE  
TITANIUM DIOXIDE  
ISOPROPYL ALCOHOL  
FERRIC OXIDE RED  
FERRIC OXIDE YELLOW  
Product Characteristics
Color BROWN, WHITE Score no score
Shape CAPSULE Size 16mm
Flavor Imprint Code PARLODEL5mg;102
Contains     
Packaging
# Item Code Package Description
1 NDC:63304-158-01 100 CAPSULE in 1 BOTTLE
2 NDC:63304-158-30 30 CAPSULE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA017962 12/22/2016
Labeler - Ranbaxy Pharmaceuticals Inc. (937890044)
Establishment
Name Address ID/FEI Operations
Halo Pharmaceutical Inc 829609168 MANUFACTURE(63304-962, 63304-158)
Revised: 12/2016
 
Ranbaxy Pharmaceuticals Inc.
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