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Medication Safety Issues
Sound-alike/look-alike issues:
Bromocriptine may be confused with benztropine, brimonidine
Cycloset® may be confused with Glyset®
Parlodel® may be confused with pindolol, Provera®
Pronunciation
(broe moe KRIP teen)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of hyperprolactinemia associated with amenorrhea with or without galactorrhea, infertility, or hypogonadism; treatment of prolactin-secreting adenomas; treatment of acromegaly; treatment of Parkinson's disease
Use: Unlabeled/Investigational
Neuroleptic malignant syndrome
Pregnancy Risk Factor
B
Pregnancy Considerations
No evidence of teratogenicity or fetal toxicity in animal studies. Bromocriptine is used for ovulation induction in women with hyperprolactinemia. In general, therapy should be discontinued if pregnancy is confirmed unless needed for treatment of macroprolactinoma. Data collected from women taking bromocriptine during pregnancy suggest the incidence of birth defects is not increased with use. However, the majority of women discontinued use within 8 weeks of pregnancy. Women not seeking pregnancy should be advised to use appropriate contraception.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
A previous indication for prevention of postpartum lactation was withdrawn voluntarily by the manufacturer following reports of serious adverse reactions, including stroke, MI, seizures, and severe hypertension. Based on the risk/benefit assessment, other treatments should be considered for lactation suppression.
Contraindications
Hypersensitivity to bromocriptine, ergot alkaloids, or any component of the formulation; ergot alkaloids are contraindicated with potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); uncontrolled hypertension; severe ischemic heart disease or peripheral vascular disorders; pregnancy (risk to benefit evaluation must be performed in women who become pregnant during treatment for acromegaly, prolactinoma, or Parkinson's disease - hypertension during treatment should generally result in efforts to withdraw)
Warnings/Precautions
Concerns related to adverse effects:
• Cardiac valvular fibrosis: Ergot alkaloids and derivatives have been associated with fibrotic valve thickening (eg, aortic, mitral, tricuspid); usually associated with long-term, chronic use.
• Cardiovascular effects: Symptomatic hypotension may occur in a significant number of patients. In addition, hypertension, seizures, MI, and stroke have been rarely associated with therapy. 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).
• Impulse control disorders: Dopamine agonists used for Parkinson's disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.
• Melanoma: Risk for melanoma development is increased in Parkinson's disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed.
• Pleural/retroperitoneal fibrosis: Rare cases of pleural and/or retroperitoneal fibrosis have been reported with prolonged daily use.
• Sedation: Sudden sleep onset and somnolence have been reported with use, primarily in patients with Parkinson's disease. Patients must be cautioned about performing tasks which require mental alertness.
Disease-related concerns:
• Acromegaly: Appropriate use: In the treatment of acromegaly, discontinuation is recommended if tumor expansion occurs during therapy. Digital vasospasm (cold sensitive) may occur in some patients with acromegaly; may require dosage reduction.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease (myocardial infarction, arrhythmia). Should not be used postpartum in women with coronary artery disease or other cardiovascular disease; use to control or prevent lactation or in patients with uncontrolled hypertension is not recommended.
• Dementia: Use with caution in patients with dementia.
• Hepatic impairment: Safety and efficacy have not been established in patients with hepatic impairment.
• Macroadenomas: Discontinuation of therapy in patients with macroadenomas has been associated with rapid regrowth of tumor and increased prolactin serum levels.
• Parkinson's disease: Safety has not been established for use >2 years in patients with Parkinson's disease.
• Peptic ulcer disease: Use with caution in patients with peptic ulcer disease.
• Psychosis: Use with caution in patients with psychosis.
• Renal disease: Safety and efficacy have not been established in patients with renal impairment.
Concurrent drug therapy issues:
• Antihypertensives: Concurrent antihypertensives or drugs which may alter blood pressure should be used with caution.
• Levodopa: Concurrent use with levodopa has been associated with an increased risk of hallucinations; consider dosage reduction and/or discontinuation in patients with hallucinations. Hallucinations may require weeks to months before resolution.
Special populations:
• Pediatrics: Safety and effectiveness have not been established in children <11 years of age for pituitary adenoma.
• Pregnancy: Patients who receive during and immediately following pregnancy as a continuation of previous therapy (eg, acromegaly) should be closely monitored for cardiovascular effects.
Other warnings/precautions:
• Pituitary function evaluation: Complete evaluation of pituitary function should be completed prior to initiation of treatment.
• Visual monitoring: 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.
Adverse Reactions
Note: Frequency of adverse effects may vary by dose and/or indication.
>10%:
Central nervous system: Dizziness, headache
Gastrointestinal: Constipation, nausea
1% to 10%:
Cardiovascular: Hypotension (including postural/orthostatic), Raynaud's syndrome exacerbation, syncope
Central nervous system: Drowsiness, fatigue, lightheadedness
Gastrointestinal: Abdominal cramps, anorexia, diarrhea, dyspepsia, GI bleeding, vomiting, xerostomia
Neuromuscular & skeletal: Digital vasospasm
Respiratory: Nasal congestion
Frequency not defined, postmarketing, and/or case reports: Abdominal discomfort, alcohol potentiation, alopecia, anxiety, arrhythmia, ataxia, blepharospasm, blurred vision, bradycardia, cerebrospinal fluid rhinorrhea, cold tolerance decreased, confusion, constrictive pericarditis, delusional psychosis, depression, dyskinesia, dysphagia, dyspnea, ear tingling, epileptiform seizure, ergotism, erythromelalgia, facial pallor, faintness, hallucinations, heavy headedness, insomnia, involuntary movements, lassitude, lethargy, lightheadedness, mottling of skin, muscle cramps, nervousness, nightmares, “on-off” phenomenon, paranoia, paresthesia, pericardial effusion, peripheral edema, pleural effusion, pleural/pulmonary fibrosis, psychomotor agitation/excitation, rash, sleep requirement decreased, sluggishness, urinary frequency, urinary retention, vasovagal attack, ventricular tachycardia, vertigo, visual disturbance, weakness
Withdrawal reactions: Abrupt discontinuation has resulted in rare cases of a withdrawal reaction with symptoms similar to neuroleptic malignant syndrome.
Postmarketing and/or case reports: Reported with dopamine agonists: Impulsive/compulsive behaviors (eg, pathological gambling, hypersexuality, binge eating)
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Inhibits CYP1A2 (weak), 3A4 (weak)
Drug Interactions
Alpha-/Beta-Agonists: May enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. Exceptions: Dipivefrin. Risk C: Monitor therapy
Antipsychotics (Atypical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Antipsychotics (Typical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
CycloSPORINE: Bromocriptine may increase the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Efavirenz: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, the risk for peripheral vasospasm and ischemia may be increased. Risk X: Avoid combination
Itraconazole: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Macrolide Antibiotics: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically leading the development of ergotism. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Posaconazole: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Protease Inhibitors: May decrease the metabolism of Ergot Derivatives. Risk X: Avoid combination
Serotonin 5-HT1D Receptor Agonists: Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Sibutramine: May enhance the serotonergic effect of Ergot Derivatives. This may cause serotonin syndrome. Risk X: Avoid combination
Voriconazole: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase GI side effects or ethanol intolerance).
Herb/Nutraceutical: St John's wort may decrease bromocriptine levels.
Mechanism of Action
Semisynthetic ergot alkaloid derivative and a dopamine receptor agonist which activates postsynaptic dopamine receptors in the tuberoinfundibular (inhibiting pituitary prolactin secretion) and nigrostriatal pathways (enhancing coordinated motor control).
Pharmacodynamics/Kinetics
Onset of action: Prolactin decreasing effect: 1-2 hours
Protein binding: 90% to 96%
Metabolism: Primarily hepatic via CYP3A; extensive first-pass biotransformation
Bioavailability: 28%
Half-life elimination: Biphasic: Terminal: 15 hours (range 8-20 hours)
Time to peak, serum: 1-3 hours
Excretion: Feces; urine (2% to 6% as unchanged drug and metabolites)
Dosage
Oral:
Children: Hyperprolactinemia:
11-15 years (based on limited information): Initial: 1.25-2.5 mg daily; dosage may be increased as tolerated to achieve a therapeutic response (range: 2.5-10 mg daily).
?16 years: Refer to adult dosing
Adults:
Parkinsonism: 1.25 mg twice daily, increased by 2.5 mg/day in 2- to 4-week intervals (usual dose range is 30-90 mg/day in 3 divided doses; maximum: 100 mg/day), though elderly patients can usually be managed on lower doses
Neuroleptic malignant syndrome (unlabeled use): 2.5-10 mg every 6-8 hours; continue therapy until NMS is controlled, then taper slowly
Acromegaly: Initial: 1.25-2.5 mg daily increasing by 1.25-2.5 mg daily as necessary every 3-7 days; usual dose: 20-30 mg/day (maximum: 100 mg/day)
Hyperprolactinemia: Initial: 1.25-2.5 mg/day; may be increased by 2.5 mg/day as tolerated every 2-7 days until optimal response (range: 2.5-15 mg/day)
Dosing adjustment in hepatic impairment: No guidelines are available, however, adjustment may be necessary
Monitoring Parameters
Monitor blood pressure closely as well as hepatic, hematopoietic, and cardiovascular function; visual field monitoring is recommended (prolactinoma); pregnancy test during amenorrheic period; growth hormone and prolactin levels.
Dietary Considerations
May be taken with food to decrease GI distress.
Patient Education
Take exactly as directed (may be prescribed in conjunction with levodopa/carbidopa); do not change dosage or discontinue this medicine without consulting prescriber. Therapeutic effects may take several weeks or months to achieve and you may need frequent monitoring during first weeks of therapy. Take with meals if GI upset occurs, before meals if dry mouth occurs, or after eating if drooling or if nausea occurs. Take at the same time each day. Maintain adequate hydration unless instructed to restrict fluid intake; void before taking medication. Do not use alcohol, prescription or OTC sedatives, or CNS depressants without consulting prescriber. Urine or perspiration may appear darker. You may experience drowsiness (can be sudden onset), dizziness, confusion, or vision changes (use caution when driving, climbing stairs, or engaging in tasks requiring alertness until response to drug is known); loss of impulse control (possibly manifested as pathological gambling, libido increases, and/or binge eating); orthostatic hypotension (use caution when rising from sitting or lying position); constipation (increased exercise, fluids, fruit, or fiber may help); nasal congestion (consult prescriber for appropriate relief); or nausea, vomiting, loss of appetite, or stomach discomfort (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report unresolved constipation or vomiting; chest pain or irregular heartbeat; acute headache or dizziness; CNS changes (eg, hallucination, loss of memory, seizures, acute headache, nervousness); suicide ideation; painful or difficult urination; increased muscle spasticity, rigidity, or involuntary movements; changes in the appearance of skin moles, skin rash, or other unusual skin changes; or significant worsening of condition. Breast-feeding precaution: Do not breast-feed.
Geriatric Considerations
No special considerations are recommended since drug is dosed to response; however, elderly may have concomitant diseases or drug therapy which may complicate therapy.
Additional Information
Usually used with levodopa or levodopa/carbidopa to treat Parkinson's disease. When adding bromocriptine, the dose of levodopa/carbidopa can usually be decreased.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Orthostatic hypotension.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness is common; may cause hallucinations
Mental Health: Effects on Psychiatric Treatment
Used to treat neuroleptic malignant syndrome and cocaine abuse; fluvoxamine and nefazodone may increase bromocriptine concentrations; monitor for hypotension, headache, nausea
Nursing: Physical Assessment/Monitoring
Monitor blood pressure at beginning of therapy and periodically during course of treatment. Assess therapeutic effectiveness (eg, mental status, involuntary movements) and adverse reactions at beginning of therapy and periodically throughout therapy. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 5 mg
Parlodel®: 5 mg
Tablet: 2.5 mg
Parlodel® SnapTabs®: 2.5 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Bromocriptine Mesylate)
5 mg (30): $131.00
Capsules (Parlodel)
5 mg (30): $234.80
Tablets (Bromocriptine Mesylate)
2.5 mg (30): $61.99
Tablets (Parlodel)
2.5 mg (30): $148.76
References
Dackis CA and Gold MS, “Bromocriptine as Treatment of Cocaine Abuse,” Lancet, 1985, 1(8438):1151-2.
de Groot AN, van Dongen PW, Vree TB, et al, “Ergot Alkaloids. Current Status and Review of Clinical Pharmacology and Therapeutic Use Compared With Other Oxytocics in Obstetrics and Gynaecology,” Drugs, 1998, 56(4):523-35.
Factor SA, “Current Status of Symptomatic Medical Therapy in Parkinson's Disease,” Neurotherapeutics, 2008, 5(2):164-80.
Koller WC, Silver DE, and Lieberman A, “An Algorithm for the Management of Parkinson's Disease,” Neurology, 1994, 44(12 Suppl 10):1-52.
Lejoyeux M, et al, “Serotonin Syndrome: Incidence, Symptoms, and Treatment,” CNS Drugs, 1994, 2:132-43.
Melmed S and Braunstein GD, “Bromocriptine and Pleuropulmonary Disease,” Arch Intern Med, 1989, 149(2):258-9.
Molina JA, Sàinz-Artiga MJ, Fraile A, et al, “Pathologic Gambling in Parkinson's Disease: A Behavioral Manifestation of Pharmacologic Treatment,” Mov Disord, 2000, 15(5):869-72.
Molitch ME, “Management of Prolactinomas During Pregnancy,” J Reprod Med, 1999, 44(12 Suppl):1121-6.
Morgans D, “Re: Parlodel,” Aust N Z J Obstet Gynaecol, 1995, 35(2):228-9.
Mueller PS, Vester JW, and Fermaglich J, “Neuroleptic Malignant Syndrome. Successful Treatment With Bromocriptine,” JAMA, 1983, 249(3):386-8.
Parkes D, “Drug Therapy: Bromocriptine,” N Engl J Med, 1979, 301(16):873-8.
Stern MB, “Contemporary Approaches to the Pharmacotherapeutic Management of Parkinson's Disease: An Overview,” Neurology, 1997, 49(1 Suppl 1):2-9.
Strawn JR, Keck PE Jr, and Caroff SN, "Neuroleptic Malignant Syndrome," Am J Psychiatry, 2007, 164(6):870-6.
Watts RL, “The Role of Dopamine Agonists in Early Parkinson's Disease,” Neurology, 1997, 49(1 Suppl 1):34-48.
Weintraub D, Siderowf AD, Potenza MN, et al, “Association of Dopamine Agonist Use With Impulse Control Disorders in Parkinson Disease,” Arch Neurol, 2006, 63(7):969-73.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2009
Content last modified August 2009
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