Brand names: Cycloset, Parlodel
Drug class: Ergot-derivative Dopamine Receptor Agonists
- Antiparkinsonian Agents
- Ergot Alkaloids
ATC class: G02CB01
VA class: AU900
CAS number: 22260-51-1

Medically reviewed by Drugs.com on Apr 17, 2024. Written by ASHP.

Introduction

Ergot-derivative dopamine receptor agonist and prolactin inhibitor.

Uses for Bromocriptine

Hyperprolactinemic Disorders

Treatment of male and female dysfunctions associated with hyperprolactinemia, including amenorrhea with or without galactorrhea, hypogonadism, and infertility.

Used for treatment of prolactin-secreting adenomas (e.g., prolactinomas), which may be the underlying endocrinopathy contributing to hyperprolactinemia.

Treatment of prolactinomas may or may not be necessary depending on size of tumor. Therapy is routinely indicated for macroadenomas (tumor ≥10 mm), but not for microadenomas unless there is a compelling indication (e.g., infertility in a patient desiring pregnancy).

Dopamine agonists are considered first-line therapy of hyperprolactinemia and prolactinomas. These drugs have been shown to decrease prolactin concentrations, reduce tumor mass, and restore gonadal function.

Cabergoline usually is preferred over bromocriptine because of its longer duration of action, greater efficacy, and more favorable adverse effect profile.

Parkinsonian Syndrome

Symptomatic management of idiopathic or postencephalitic parkinsonian syndrome. However, ergot-derived dopamine agonists such as bromocriptine no longer recommended in the treatment of parkinson disease because of risks of serious adverse effects (e.g., cardiac valvulopathy); if dopamine agonist therapy is required, a nonergot-derived dopamine agonist (e.g., pramipexole, ropinirole, rotigotine) should be used.

Acromegaly

Treatment of acromegaly. However, transsphenoidal surgery is first-line treatment for this condition; in patients who cannot undergo surgery or who have persistent disease after surgery, somatostatin receptor agonists (e.g., octreotide, lanreotide) generally recommended as medical therapy of choice.

Dopamine agonists usually considered only for adjuvant medical therapy in patients with mild disease following surgery.

Type 2 Diabetes Mellitus

Rapid-release formulation (Cycloset) is used as an adjunct to diet and exercise for the management of type 2 diabetes mellitus.

Unlike traditional formulations, this dosage form was designed to deliver a brief daily interval of circulating bromocriptine in the morning to mimic the natural circadian peak in central dopaminergic activity. When used as an antidiabetic agent, bromocriptine is given in much lower dosages than those used for other indications.

Has been shown to improve glycemic control (as assessed by postprandial glucose and HbA_1c concentrations); however, magnitude of treatment effect is small.

Main benefit appears to be a reduction in postprandial hyperglycemia without increasing plasma insulin levels; also does not cause hypoglycemia. May be associated with a reduced risk of cardiovascular events; however, conclusive evidence of a macrovascular risk reduction not established.

Limited experience in combination with thiazolidinediones; efficacy in combination with insulin not confirmed.

Do not use in patients with type 1 diabetes mellitus or diabetic ketoacidosis.

Male Infertility

Has been used to increase sperm counts and restore fertility^{† [off-label]} in oligospermic men without hyperprolactinemia who are unresponsive to traditional drug therapy.

Neuroleptic Malignant Syndrome

Has been used to relieve extrapyramidal reactions, hyperthermia, and hypertension of neuroleptic malignant syndrome^{† [off-label]} (NMS) associated with neuroleptic drug therapy (e.g., haloperidol, fluphenazine).

Hepatic Encephalopathy

Has been used in the management of chronic hepatic encephalopathy^{† [off-label]}.

Postpartum Breast Engorgement

Used in the past for prevention of postpartum breast engorgement^{† [off-label]}; FDA has withdrawn this labeled use because the risk of serious, potentially fatal adverse effects outweighed the limited benefits. (See Cardiovascular Effects under Cautions.)

Bromocriptine Dosage and Administration

General

• Individualize and adjust dosage carefully; evaluate frequently during dosage adjustment to determine lowest therapeutic dosage.

• Temporary dosage reduction or discontinuance may be necessary in patients who develop intolerable adverse effects.

Hyperprolactinemic Disorders

• During initial therapy for female infertility, use a mechanical contraceptive in conjunction with bromocriptine therapy until normal ovulatory menstrual cycles have been restored; contraception can then be discontinued.

• If menstruation does not occur within 3 days of the expected date, discontinue bromocriptine and perform a pregnancy test.

• When bromocriptine is discontinued (i.e., during pregnancy) in patients with hyperprolactinemic disorders, monitor patients for tumor progression or development. (See Warnings: Pregnancy under Cautions.)

Acromegaly

• Determine serum growth hormone concentrations monthly, and adjust bromocriptine dosage based on the reduction in these concentrations and the patient’s clinical response.

• If an adequate response is not apparent after a brief trial with the drug and/or dosage adjustment and clinical evaluation, consider discontinuance of bromocriptine.

• Withdraw therapy (4- to 8-week period is usually adequate) annually in patients undergoing radiation therapy of the pituitary to determine if continued therapy with the drug and/or radiation is necessary. If signs and/or symptoms of acromegaly recur or growth hormone concentrations increase during this period, consider additional bromocriptine therapy.

Administration

Oral Administration

Administer orally with food.

Dosage

Available as bromocriptine mesylate; dosage expressed in terms of bromocriptine.

Pediatric Patients

Hyperprolactinemic Disorders

Prolactin-secreting Adenomas

Oral

Children ≥11 years of age: Initially, 1.25–2.5 mg daily. May increase as tolerated until therapeutic response achieved. Usual dosage range is 2.5–10 mg daily.

Adults

Hyperprolactinemic Disorders

Amenorrhea, Galactorrhea, Female Infertility

Oral

Initially, 1.25–2.5 mg daily. May increase dosage by 2.5 mg every 2–7 days, as tolerated, until therapeutic response achieved. Usual dosage range is 2.5–15 mg daily; up to 30 mg daily has been required in some patients with amenorrhea and/or galactorrhea.

Hypogonadism and Galactorrhea in Males

Oral

Initially, 1.25–2.5 mg daily. May increase dosage by 2.5 mg every 2–7 days, as tolerated, until therapeutic response achieved. Usual dosage range is 2.5–15 mg daily; up to 40 mg daily has been required in some patients.

Prolactin-secreting Adenomas

Oral

Initially, 1.25–2.5 mg daily. May increase dosage by 2.5 mg every 2–7 days, as tolerated, until therapeutic response achieved. Usual dosage range is 2.5–15 mg daily.

Parkinsonian Syndrome

Oral

Initially, 1.25 mg twice daily. If needed, may increase dosage by 2.5 mg daily every 14–28 days; do not exceed 100 mg daily.

Assess patient’s therapeutic response at 2-week intervals to ensure lowest effective dosage is not exceeded.

In patients receiving levodopa, continue the drug if possible during initiation of bromocriptine. If dosage reduction of levodopa is required because of adverse effects, may increase daily dosage of bromocriptine gradually in 2.5-mg increments.

Acromegaly

Oral

Initially, 1.25–2.5 mg at bedtime for 3 days. May increase dosage by 1.25–2.5 mg daily at 3- to 7-day intervals, as tolerated, until desired therapeutic benefit achieved.

Reevaluate patients monthly; adjust dosage based on reduction of growth hormone or clinical response. Usual dosage range is 20–30 mg daily; do not exceed 100 mg daily. Dosages of 20–60 mg have been administered daily in divided doses.

Type 2 Diabetes Mellitus (Cycloset)

Oral

Recommended dosage is 1.6–4.8 mg once daily administered in the morning within 2 hours of awakening.

Initiate with 0.8 mg (1 tablet) once daily; increase by 0.8 mg (1 tablet) at weekly intervals until maximum tolerated dosage is reached (up to 4.8 mg once daily).

In patients receiving concomitant therapy with a moderate CYP3A4 inhibitor (e.g., erythromycin), do not exceed a bromocriptine dosage of 1.6 mg once daily.

Neuroleptic Malignant Syndrome† [off-label]

Oral

2.5–5 mg 2–6 times daily.

Hepatic Encephalopathy†

Oral

Initially, 1.25 mg daily; increase dosage by 1.25 mg daily every third day up to a total maintenance dosage of 15 mg daily.

Prescribing Limits

Adults

Acromegaly

Oral

Do not exceed 100 mg daily.

Parkinsonian Syndrome

Oral

Safety of dosages >100 mg daily not established. Safety of therapy for >2 years not established.

Type 2 Diabetes Mellitus (Cycloset)

Oral

Maximum 4.8 mg daily.

Special Populations

Hepatic Impairment

Decreased clearance; dosage adjustment may be necessary. (See Elimination under Pharmacokinetics.)

Cautions for Bromocriptine

Contraindications

• Uncontrolled hypertension. (See Cardiovascular Effects under Cautions.)

• Known sensitivity to ergot alkaloids.

• Known hypersensitivity to bromocriptine or any ingredient in the formulation.

• Patients with syncopal migraines.

• Nursing women.

Warnings/Precautions

Warnings

Pregnancy

Safe use during pregnancy not established. Mechanical contraceptive measures recommended for women not seeking pregnancy or those with large adenomas. Perform pregnancy test at least every 4 weeks in amenorrheic women and, once menstruation has been reinstated, whenever a menstrual period is missed.

Possible sudden enlargement of underlying prolactin-secreting pituitary tumors in women with hyperprolactinemic disorders who become pregnant and discontinue bromocriptine therapy; may result from normal increases in pituitary size during pregnancy. May cause optic nerve compression, visual impairment, or blindness, which usually disappear after delivery; regular visual field checks recommended. Diabetes insipidus and pituitary apoplexy also may occur. Prior to initiating therapy for amenorrhea/galactorrhea and infertility, carefully evaluate the pituitary to rule out pituitary tumors.

Discontinue therapy immediately if pregnancy occurs during therapy for hyperprolactinemic disorders and carefully observe women throughout pregnancy for signs and symptoms of tumor progression. If reinstitution of therapy is required to control a rapidly expanding macroadenoma and a hypertensive disorder associated with pregnancy occurs, consider risks and benefits of continuing bromocriptine therapy. (See Cardiovascular Effects under Cautions.)

If pregnancy occurs in a woman receiving therapy for acromegaly or parkinsonian syndrome, discontinue therapy unless bromocriptine therapy is medically necessary. If therapy is continued and a hypertensive disorder of pregnancy occurs, discontinue therapy unless bromocriptine withdrawal is medically contraindicated.

Only continue bromocriptine during the postpartum period in women with a cardiovascular disease history if withdrawal is considered medically contraindicated; carefully observe the patient.

Somnolence

May cause somnolence.

Episodes of falling asleep while engaged in activities of daily living, sometimes without warning or awareness, reported, particularly in patients with parkinson disease. Consider dosage reduction or treatment discontinuance if these effects occur; advise patients not to drive and to avoid other potentially dangerous activities.

Cardiovascular Effects

Symptomatic hypotension reported, especially during initial treatment; use caution, especially during the first days of treatment. Contraindicated in patients with syncopal migraine since bromocriptine increases likelihood of such patients developing a hypotensive episode.

Hypertension (sometimes developing with initiation of therapy but often during the second week), seizures, and potentially fatal strokes reported, mostly in postpartum women. Acute MI reported rarely. Seizures and strokes usually preceded by a constant and severe headache hours to days prior to event and may be preceded by visual disturbances (blurred vision, transient cortical blindness).

Discontinue therapy immediately and evaluate patient promptly if hypertension; severe, progressive, or unremitting headache (with or without visual disturbances); or evidence of CNS toxicity occurs.

Periodic monitoring of BP recommended, especially during the first few weeks of therapy.

Use with caution in patients with a history of cardiovascular disease or MI with residual atrial, nodal, or ventricular arrhythmia.

Fibrotic Effects

Pleural and pericardial effusions, constrictive pericarditis, and pleural and pulmonary fibrosis reported, especially in patients receiving high-dose, long-term therapy; usually resolves slowly with discontinuance of therapy. Consider discontinuance of therapy if these disorders occur.

Observe patients receiving long-term (e.g., 6–36 months), high-dose (e.g., 20–100 mg daily) therapy for pulmonary changes (e.g., infiltrates, effusion, and thickening of the pleura). Thoroughly evaluate unexplained pleuropulmonary disorders and consider discontinuance of therapy.

Retroperitoneal fibrosis reported rarely in patients receiving long-term (e.g., 2–10 years), high-dose (30–140 mg daily) therapy. Monitor for manifestations (e.g., back pain, lower extremity edema, impaired kidney function); discontinue therapy if fibrotic changes are diagnosed or suspected.

General Precautions

Impulse Control and Compulsive Behaviors

Intense urges (e.g., urge to gamble, increased sexual urges, intense urges to spend money uncontrollably, other intense urges) and inability to control these urges reported in some patients receiving dopaminergic drugs.

Consider reducing dosage or discontinuing therapy if a patient develops such urges. (See Advice to Patients.)

Nervous System Effects

Confusion and mental disturbances may occur in patients with parkinsonian syndrome receiving high-dose therapy.

Visual or auditory hallucinations reported in patients with parkinsonian syndrome. Use with caution in patients with a history of psychosis; avoid use in patients with severe psychotic disorders.

CSF rhinorrhea reported rarely in patients with prolactin-secreting adenomas who previously underwent transsphenoidal surgery and/or radiation therapy and who were receiving the drug for tumor recurrence; may also occur in patients with previously untreated prolactinoma that extends into the sphenoid sinus.

Lactose Intolerance

Use not recommended in patients with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption.

Ocular Effects

Secondary visual field loss due to chiasmal herniation may occur in patients with macroprolactinoma effectively treated for hyperprolactinemia. Monitor patients and consider decreasing dosage if this occurs.

Relative efficacy of bromocriptine therapy versus surgery in preserving the visual fields in patients with hyperprolactinemic disorders not known. Patients with rapidly progressing visual field loss should be evaluated by a neurosurgeon.

Digital Vasospasm

Cold-sensitive digital vasospasm reported in patients being treated for acromegaly; usually resolves following a reduction in dosage and may be prevented by keeping fingers warm.

Growth Hormone-secreting Tumors

Possible expansion of growth hormone-secreting tumors in patients with acromegaly. Careful monitoring recommended; if evidence of tumor expansion occurs, discontinue therapy and consider alternative therapies.

Adequate Patient Monitoring

Evaluate hepatic, hematopoietic, cardiovascular, and renal function periodically in patients receiving prolonged therapy with bromocriptine.

GI Bleeding

Severe GI bleeding from peptic ulcers, sometimes fatal, reported in patients with acromegaly. Closely monitor patients with a history of peptic ulcer or GI bleeding. Thoroughly evaluate signs and symptoms of peptic ulcer; institute appropriate therapy if necessary.

Specific Populations

Pregnancy

Does not appear to be associated with fetal risk. However, use of dopamine agonists generally not recommended during pregnancy; use only if clearly needed. (See Warnings: Pregnancy under Cautions.)

Lactation

Use not recommended in nursing women because bromocriptine interferes with lactation. Some manufacturers state use in nursing women is contraindicated.

Pediatric Use

Safety and efficacy established for children ≥16 years of age for treatment of prolactin-secreting adenomas. Use in pediatric patients 11–15 years of age is supported by evidence from well-controlled clinical trials in adults and additional data in children from this age group.

Safety and efficacy not established for other uses.

Geriatric Use

In clinical trials evaluating use of bromocriptine for hyperprolactinemic disorders, acromegaly, and parkinson disease, insufficient experience to determine whether geriatric patients ≥65 years of age respond differently than younger adults; consider age-related decreases in hepatic, renal, or cardiac function in this population.

In clinical trials evaluating use of bromocriptine for type 2 diabetes mellitus, no overall differences in safety and efficacy observed between geriatric patients and younger individuals.

Hepatic Impairment

Use with caution; safety and efficacy not established. Reduced dosage may be required.

Renal Impairment

Use with caution; safety and efficacy not established.

Common Adverse Effects

Patients with hyperprolactinemia: Nausea, headache, fatigue, dizziness, lightheadedness, vomiting, abdominal cramps, constipation, diarrhea, drowsiness, nasal congestion.

Patients with acromegaly: Nausea, constipation, postural/orthostatic hypotension, anorexia, dry mouth/nasal stuffiness, indigestion/dyspepsia, digital vasospasm, drowsiness.

Patients with parkinsonian syndrome: Nausea, involuntary movements, hallucinations, confusion, “on-off” episodes, dizziness, drowsiness, faintness/fainting, vomiting, asthenia, abdominal discomfort, visual disturbance, ataxia, insomnia, depression, hypotension, shortness of breath, constipation, vertigo.

Patients with type 2 diabetes mellitus: Nausea, fatigue, dizziness, vomiting, headache.

Drug Interactions

Metabolized principally by CYP3A; potent inhibitor of CYP3A4.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: May increase plasma bromocriptine concentrations; use concomitantly with caution. Manufacturer of the rapid-release formulation (Cycloset) advises to avoid concomitant use of potent CYP3A4 inhibitors; reduced dosage may be required if used concomitantly with moderate CYP3A4 inhibitors. (See Type 2 Diabetes Mellitus under Dosage and Administration.)

Inducers of CYP3A4: May decrease plasma bromocriptine concentrations; use concomitantly with caution.

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP3A4 substrates: Bromocriptine not expected to alter metabolism of CYP3A4 substrates.

Protein-bound Drugs

Bromocriptine may increase the unbound fraction of other highly protein-bound drugs (e.g., salicylates, sulfonamides, chloramphenicol, probenecid); may alter efficacy or safety of concomitantly administered drug.

Specific Drugs

Bromocriptine Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability of conventional formulation is 28%, with peak plasma concentration usually attained within 1–3 hours.

Bioavailability of rapid-release formulation (Cycloset) is 65–95%; peak plasma concentrations are achieved in approximately 53 minutes when given under fasting conditions and approximately 90–120 minutes when given with a high-fat meal.

Onset and Duration

Following oral administration of a single 1.25- to 5-mg dose (as a conventional dosage form), serum prolactin decreases within 2 hours, is maximally decreased at 8 hours, and remains decreased at 24 hours.

In hyperprolactinemic patients, maximum obtainable reduction of serum prolactin usually occurs within the first 4 weeks of therapy.

In patients with acromegaly, a single oral dose of 2.5 mg substantially reduces plasma growth hormone within 1–2 hours; decreased concentrations persist for at least 4–5 hours.

Distribution

Extent

Does not distribute appreciably into erythrocytes.

Plasma Protein Binding

90–96% (mainly albumin).

Elimination

Metabolism

Undergoes extensive first-pass biotransformation in the liver, primarily via CYP3A4.

Elimination Route

Bromocriptine and its metabolites eliminated principally (82–85%) in feces via biliary excretion and to a lesser extent (6%) in urine.

Half-life

Biphasic; terminal half-life of conventional formulation is approximately 15 hours and elimination half-life of rapid-release formulation is approximately 6 hours.

Special Populations

Hepatic impairment may increase plasma bromocriptine concentrations.

Stability

Storage

Oral

Conventional Capsules and Tablets

Tight, light-resistant containers at 20–25°C (may be exposed to 15–30°C).

Rapid-release Tablets (Cycloset)

Tight, light-resistant containers at 20–25°C.

Actions

• A dopamine receptor agonist that activates postsynaptic dopamine receptors that modulate the secretion of prolactin from the anterior pituitary.

• Substantially reduces serum prolactin concentrations by inhibiting release of prolactin from the anterior pituitary gland; directly affects the pituitary and/or stimulates postsynaptic dopamine receptors in the hypothalamus to release prolactin-inhibitory factor via a complicated catecholamine pathway.

• Causes transient increases in somatropin (growth hormone) secretion in individuals with normal growth hormone concentrations; paradoxically causes sustained suppression of growth hormone secretion in patients with acromegaly.

• Relieves symptoms of parkinsonism by directly stimulating dopamine receptors in the corpus striatum; dysregulation of brain serotonin activity may also occur.

Advice to Patients

• Risk of dizziness, drowsiness, or faintness; use caution when driving or operating machinery.

• Risk of somnolence; possibility of falling asleep during activities of daily living. If this occurs, patients should not drive or participate in potentially dangerous activities until episodes resolve.

• Importance of immediately informing clinician if persistent watery nasal discharge occurs in patients being treated for macroadenoma or in patients who have had recent transsphenoidal surgery.

• Importance of informing clinician if new or increased gambling urges, sexual urges, or other urges occur while receiving bromocriptine.

• Advise patients being treated for macroadenoma that discontinuance of bromocriptine may result in rapid regrowth of tumor and recurrence of original symptoms.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses, such as hypertension or hypotension.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of using a method of contraception and monitoring regular pregnancy tests in patients treated for amenorrhea, as pregnancy may occur prior to the return of menses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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