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Bromocriptine Mesylate

Pronunciation

Class: Ergot-derivative Dopamine Receptor Agonists
ATC Class: G02CB01
VA Class: AU900
CAS Number: 22260-51-1
Brands: Parlodel

Introduction

Ergot-derivative dopamine receptor agonist and prolactin inhibitor.a b

Uses for Bromocriptine Mesylate

Hyperprolactinemic Disorders

Treatment of male and female dysfunctions associated with hyperprolactinemia, including amenorrhea and/or galactorrhea, hypogonadism, and infertility.a b

Used in patients with prolactin-secreting adenomas (e.g., prolactinoma), including macroadenomas, to decrease tumor size; may be used prior to surgery in patients undergoing excision of the tumor (adenectomy).a b

Treatment of female infertility associated with hyperprolactinemia; used to induce ovulation in appropriately selected anovulatory women.b

Treatment of hypogonadism and galactorrhea that persist following radiation therapy or surgery in hyperprolactinemic males with prolactin-secreting adenomas and adequate testosterone concentrations.a b Some clinicians consider bromocriptine the treatment of choice for reduction of large tumors (macroadenomas).b

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Parkinsonian Syndrome

Symptomatic management of idiopathic or postencephalitic parkinsonian syndrome.a b

Used as an adjunct to levodopa for the symptomatic management of parkinsonian syndrome in patients with advanced disease.111 112 a

Has been used as monotherapy for initial symptomatic management of parkinsonian syndrome.111 Most clinicians would use levodopa for initial therapy in individuals >70 years of age (less likely than younger individuals to develop levodopa-related motor complications and because of concerns about cognitive dysfunction), in patients with cognitive impairment, and in those with severe disease.111 A dopamine receptor agonist may be preferred for initial therapy in patients ≤70 years of age.111

Acromegaly

Treatment of acromegaly, alone or as adjunctive therapy with pituitary irradiation or surgery.a b

Male Infertility

Has been used to increase sperm counts and restore fertility in oligospermic men without hyperprolactinemia who are unresponsive to traditional drug therapy.b

Neuroleptic Malignant Syndrome

Has been used to relieve extrapyramidal reactions, hyperthermia, and hypertension of neuroleptic malignant syndrome (NMS) associated with neuroleptic drug therapy (e.g., haloperidol, fluphenazine).b

Hepatic Encephalopathy

Has been used in the management of chronic hepatic encephalopathy.b

Postpartum Breast Engorgement

Used in the past for prevention of postpartum breast engorgement;106 b FDA has withdrawn approval of bromocriptine for this indication because the risk of serious, potentially fatal adverse effects100 102 104 107 108 outweigh the limited benefits associated with this use.101 103 (See Cardiovascular Effects under Cautions.)

Bromocriptine Mesylate Dosage and Administration

General

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

  • Temporary dosage reduction or discontinuance may be necessary in patients developing intolerable adverse effects.b

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

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.a b

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

Parkinsonian Syndrome

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

Acromegaly

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

  • 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.a b

  • 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.a b If signs and/or symptoms of acromegaly recur or growth hormone concentrations increase during this period, consider additional bromocriptine therapy.a b

Administration

Oral Administration

Administer orally with food.a b

Dosage

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

Pediatric Patients

Hyperprolactinemic Disorders
Prolactin-secreting Adenomas
Oral

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

Adults

Hyperprolactinemic Disorders
Amenorrhea, Galactorrhea, Female Infertility
Oral

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

Hypogonadism and Galactorrhea in Males
Oral

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

Prolactin-secreting Adenomas
Oral

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

Parkinsonian Syndrome
Oral

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

If levodopa dosage reduced because of adverse effects, may increase daily dosage of bromocriptine gradually in 2.5-mg increments.a b

Acromegaly
Oral

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

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

Neuroleptic Malignant Syndrome
Oral

2.5–5 mg 2–6 times daily.b

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.b

Prescribing Limits

Safety of dosages >100 mg daily not established.a b

Adults

Parkinsonian Syndrome
Oral

Maximum 100 mg daily.a b Safety of therapy for >2 years not established.a b

Special Populations

Hepatic Impairment

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

Cautions for Bromocriptine Mesylate

Contraindications

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

  • Known sensitivity to ergot alkaloids.a b

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

Warnings/Precautions

Warnings

Pregnancy

Mechanical contraceptive measures recommended for women not seeking pregnancy or those with large adenomas.a b Perform pregnancy test every 4 weeks in amenorrheic women and, once menses are reinstated, whenever a menstrual period is missed.a b

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.a b May cause optic nerve compression, visual impairment, or blindness, which usually disappear after delivery; regular visual field checks recommended.a b Diabetes insipidus and pituitary apoplexy also may occur.a b Prior to initiating therapy for amenorrhea/galactorrhea and infertility, carefully evaluate the pituitary including gadolinium-enhanced MRI to rule out pituitary tumors.a b c

Discontinue therapy immediately if pregnancy occurs during therapy for hyperprolactinemic disorders and carefully observe women throughout pregnancy for signs and symptoms of tumor progression.a b 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.a (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.a If therapy is continued and a hypertensive disorder of pregnancy occurs, discontinue therapy unless bromocriptine withdrawal is medically contraindicated.a b

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

Somnolence

Episodes of falling asleep while engaged in activities of daily living, sometimes without warning or awareness, have been reported, particularly in patients with parkinsonian syndrome.a Consider dosage reduction or treatment discontinuance if these effects occur.a

Cardiovascular Effects

Symptomatic hypotension reported, especially during initial treatment; use caution, especially during the first days of treatment.a b

Hypertension (sometimes developing with initiation of therapy but often during the second week), seizures, and potentially fatal strokes reported, mostly in postpartum women.a Acute MI reported rarely.a

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).a b

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.a b

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

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

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.a b Consider discontinuance of therapy if these disorders occur.a

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).a b Thoroughly evaluate unexplained pleuropulmonary disorders and consider discontinuance of therapy.a

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

General Precautions

Nervous System Effects

Confusion and mental disturbances may occur in patients with parkinsonian syndrome receiving high-dose therapy; usually resolve within 2–3 weeks after discontinuance.a Use caution in patients who manifest mild dementia.a

Visual or auditory hallucinations reported in patients with parkinsonian syndrome; hallucinations usually resolve following dosage reduction, but discontinuance of drug may occasionally be necessary.a b Rarely, hallucinations may persist for several weeks following discontinuance of the drug.a b Use with caution in patients with a history of psychosis.a

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.a b

Lactose Intolerance

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

Ocular Effects

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

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

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.a

Growth Hormone-secreting Tumors

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

Adequate Patient Monitoring

Evaluate hepatic, hematopoietic, cardiovascular, and renal function periodically in patients receiving prolonged therapy with bromocriptine (e.g., treatment of parkinsonian syndrome).a

GI Bleeding

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

Specific Populations

Pregnancy

Category B.a (See Warnings: Pregnancy under Cautions.)

Lactation

Use not recommended in nursing women because bromocriptine interferes with lactation.a b

Pediatric Use

Safety and efficacy established for children ≥16 years of age for treatment of prolactin-secreting adenomas.a However, bromocriptine has been evaluated in well-controlled clinical trials in children ≥11 years of age.a

Safety and efficacy not established for other uses.a

Geriatric Use

Insufficient experience in clinical trials with patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; consider age-related decreases in hepatic, renal, or cardiac function in this population.a b

Hepatic Impairment

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

Renal Impairment

Use with caution; safety and efficacy not established.a b

Common Adverse Effects

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

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

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.a

Interactions for Bromocriptine Mesylate

Metabolized principally by CYP3A; potent inhibitor of CYP3A4.a

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma bromocriptine concentrations).a

Drugs Metabolized by Hepatic Microsomal Enzymes

Potent substrates of CYP3A4: Potential pharmacokinetic interaction (increased plasma substrate concentrations).a However, not expected to alter metabolism of CYP3A4 substrates, due to low free concentrations of bromocriptine.a

Drugs That Increase Prolactin Concentrations

Potential inhibition of bromocriptine’s effectiveness in reducing serum prolactin concentrations.a

Specific Drugs

Drug

Interaction

Comments

Alcohol

May potentiate adverse effects of bromocriptinea

Possible decreased alcohol toleranceb

Limit alcohol intakea b

Antidepressants, tricyclics (amitriptyline, imipramine)

Potential reduced efficacy of bromocriptine b

Consider increasing bromocriptine dosageb

Antifungals, azoles

Possible interference with bromocriptine metabolisma

Use concomitantly with cautiona

Antihypertensives

Potential additive hypotensive effectsa b

Careful adjustment of antihypertensive dosage may be necessarya b

Use with cautiona b

Antipsychotic agents (haloperidol, phenothiazines)

Possible reduced efficacy of bromocriptinea b

Increased bromocriptine dosage may be required if used concomitantlyb

Butyrophenones (e.g., droperidol)

Potential reduced bromocriptine concentrationsa b

Consider increasing bromocriptine dosageb

Dopamine antagonists (e.g., metoclopromide, pimozide)

Possible reduced efficacy of bromocriptinea

Ergot alkaloids

Potential for severe adverse effects (e.g., hypertension, myocardial infarction)a b (see Cardiovascular Effects under Cautions)

Concomitant use not recommendeda b

HIV protease inhibitors

Possible interference with bromocriptine metabolisma

Use concomitantly with cautiona

Levodopa

Potential additive therapeutic and neurologic effectsb

May be used to therapeutic advantage; consider decreasing levodopa dosageb

Macrolide antibiotics (e.g., erythromycin)

Increased plasma bromocriptine concentrationsa

Methyldopa

Possible reduced efficacy of bromocriptineb

Increased bromocriptine dosage may be required if used concomitantlyb

Octreotide

Increased concentrations of bromocriptinea

Reserpine

Possible reduced efficacy of bromocriptinea b

Increased bromocriptine dosage may be required if used concomitantlyb

Bromocriptine Mesylate Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability 28%, with peak plasma concentration usually attained within 1–3 hours.a

Onset

Following oral administration, onset of prolactin-lowering effect begins within 1–2 hours of ingestion, with maximal benefit within 5–10 hours.a Parkinsonian effects may begin 30–90 minutes after ingestion, with maximal benefit within approximately 2 hours.b

Duration

Maximum prolactin-lowering effects generally persist for 8–12 hours.a

Distribution

Extent

Does not distribute appreciably into erythrocytes.a b

Plasma Protein Binding

90–96% (mainly albumin).a

Elimination

Metabolism

Undergoes extensive first-pass biotransformation in the liver, primarily via CYP3A and hydroxylation, to form inactive metabolites.a b

Elimination Route

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

Half-life

Biphasic; terminal half-life is approximately 15 hours.a

Special Populations

Hepatic impairment decreases elimination, resulting in increased plasma bromocriptine concentrations.a

Stability

Storage

Oral

Capsules and Tablets

Tight, light-resistant containers at <25°C.a

Actions

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

  • 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.b

  • 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.a b

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

Advice to Patients

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

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

  • 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.a

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

  • 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.a

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

  • 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.a

  • 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.

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

Bromocriptine Mesylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

5 mg (of bromocriptine)*

Bromocriptine Mesylate Tablets

Sandoz

Parlodel

Novartis

Tablets

2.5 mg (of bromocriptine)*

Bromocriptine Mesylate Tablets

Lek, Sandoz

Parlodel SnapTabs (with povidone; scored)

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Bromocriptine Mesylate 2.5MG Tablets (PADDOCK): 30/$64.99 or 90/$174.97

Bromocriptine Mesylate 5MG Capsules (MYLAN): 30/$135.99 or 90/$385.97

Cycloset 0.8MG Tablets (SANTARUS): 30/$67.99 or 90/$185.40

Parlodel 2.5MG Tablets (NOVARTIS): 30/$165.99 or 90/$497.98

Parlodel 5MG Capsules (NOVARTIS): 30/$259.99 or 90/$709.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

100. Anon. Sandoz withdrawing Parlodel postpartum lactation suppression indication. Prescription Pharm Biotechnol. 1994; 56(Aug 22):T&G1-2.

101. Anon. Bromocriptine indication withdrawn. FDA Med Bulletin. 1994; 24:2.

102. Anon. Sandoz will halt promotion of bromocriptine for suppression of lactation. Am J Hosp Pharm. 1994; 51:2626.

103. Hartwig SC, Smeenk DA, Michaels MR. Drug-use evaluation program for postpartum bromocriptine therapy. Am J Hosp Pharm. 1990; 47:2514-5. [PubMed 2278264]

104. Larrazet F, Spaulding C, Lobreau HJ et al. Possible bromocriptine-induced myocardial infarction. Ann Intern Med. 1993; 118:199-200. [IDIS 308704] [PubMed 8417637]

105. Sandoz, East Hanover, NJ: Personal communication.

106. Sandoz. Parlodel (bromocriptine mesylate) Snap-Tabs tablets and capsules prescribing information dated Sep 1993. In: Physicians’ desk reference. 49th ed. Montvale, NJ: Medical Economics Company, Inc. 1994:2178-80.

107. Rothman KJ, Funch DP, Dreyer NA. Bromocriptine and puerperal seizures. Epidemiology. 1990; 1:232-8. [PubMed 2081258]

108. Eickman FM. Recurrent myocardial infarction in a postpartum patient receiving bromocriptine. Clin Cardiol. 1992; 15:781-3. [PubMed 1395192]

109. Gittelman D. Bromocriptine associated with postpartum hypertension, seizures, and pituitary hemorrhage. Gen Hosp Psychiatry. 1991; 13:278-80. [PubMed 1874430]

110. Food and Drug Administration. Sandoz Pharmaceutical Corp.; Bromocriptine mesylate (Parlodel); withdrawal of approval of the indication for the prevention of physiological lactation. [Docket No. 94N-0304.] Fed Regist. 1995; 60:3404-5.

111. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001; 56:S1-S88.

112. Anon. Initial treatment of Parkinson’s disease: wait just a minute. Med Lett Drugs Ther. 2001; 43:59-60. [PubMed 11445778]

a. Novartis. Parlodel (bromocriptine mesylate) SnapTabs tablets and capsules prescribing information. Suffern, NY; 2006 May.

b. AHFS drug information 2006. McEvoy GK, ed. Bromocriptine mesylate. Bethesda, MD: American Society of Health-System Pharmacists; 2006:3610-4.

c. Schleachte, JA. Prolactinoma. NEJM. 2007; 349;21:2035-41.

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