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Pronunciation
(broe moe KRIP teen)
Generic Available (U.S.)
Yes: Excludes Cycloset®
Index Terms
Brand Names: U.S.
Brand Names: Canada
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
Cycloset®: Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise
Use: Unlabeled
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/contraindicated
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A previous indication for prevention of postpartum lactation was withdrawn voluntarily by the manufacturer following reports of serious adverse reactions, including stroke, MI, seizures, and severe hypertension. Use during breast-feeding is specifically contraindicated in the product labeling for Cycloset®. Use in postpartum women with a history of coronary artery disease or other severe cardiovascular conditions is specifically contraindicated in the product labeling for Parlodel® (unless withdrawal of medication is medically contraindicated). 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
Additional contraindications:
Parlodel®: Uncontrolled hypertension; 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); postpartum women with a history of coronary artery disease or other severe cardiovascular conditions (unless withdrawal of medication is medically contraindicated)
Cycloset®: Syncopal migraine; breast-feeding
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.
• Diabetic ketoacidosis (DKA): Should not be used in patients with DKA due to lack of efficacy in this patient population.
• 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 extreme caution or avoid use in patients with psychosis.
• Renal disease: Safety and efficacy have not been established in patients with renal impairment.
• Type 1 diabetes mellitus: Should not be used in patients with type 1 diabetes mellitus (insulin dependent, IDDM) due to lack of efficacy in this patient population.
Concurrent drug therapy issues:
• Antidiabetic agents: There is limited efficacy of use in combination with thiazolidinediones or in combination with insulin. Combination therapy with other hypoglycemic agents may increase risk for hypoglycemic events; dose reduction of concomitant hypoglycemics may be warranted.
• Antihypertensives: Concurrent antihypertensives or drugs which may alter blood pressure should be used with caution.
• High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors and/or major CYP3A4 substrates (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.
• 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.
Dosage form specific issues:
• Interchangeability (Cycloset®): Due to a difference in the formulation and resulting pharmacokinetics of Cycloset® ("quick-release" tablet) compared to other formulations of bromocriptine, interchangeability with any other bromocriptine product is not recommended in the setting of type 2 diabetes mellitus management.
Other warnings/precautions:
• Pituitary function evaluation: Complete evaluation of pituitary function should be completed prior to initiation of treatment of any hyperprolactinemia-associated dysfunction.
• 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, fatigue, headache
Gastrointestinal: Constipation, nausea
Neuromuscular & skeletal: Weakness
Respiratory: Rhinitis
1% to 10%:
Cardiovascular: Hypotension (including postural/orthostatic), Raynaud's syndrome exacerbation, syncope
Central nervous system: Drowsiness, lightheadedness, somnolence
Endocrine & metabolic: Hypoglycemia (4%; in combination with sulfonylureas or other antidiabetic agents: 7% to 9%)
Gastrointestinal: Abdominal cramps, anorexia, diarrhea, dyspepsia, GI bleeding, vomiting, xerostomia
Neuromuscular & skeletal: Digital vasospasm
Ocular: Amblyopia
Respiratory: Nasal congestion, sinusitis
Miscellaneous: Infection, flu-like syndrome
Frequency not defined, postmarketing, and/or case reports: Abdominal discomfort, allergic reactions, alopecia, anxiety, arrhythmia, ataxia, blepharospasm, blindness (transient), blurred vision, bradycardia, cardiac valve fibrosis, cerebrospinal fluid rhinorrhea, cold extremities, cold tolerance decreased, confusion, constrictive pericarditis, delusional psychosis, depression, dyskinesia, dysphagia, dyspnea, ear tingling, epileptiform seizure, ergotism, erythromelalgia, facial pallor, faintness, gastrointestinal ulceration, hallucinations, heavy headedness, hypertension (postpartum), insomnia, lassitude, lethargy, libido increased, MI (postpartum), mottling of skin, muscle cramps, nervousness, nightmares, “on-off” phenomenon, paranoia, paresthesia, pericardial effusion, peripheral edema, pleural effusion, pleural/pulmonary fibrosis, pleurisy, psychomotor agitation/excitation, psychosis, rash, retroperitoneal fibrosis, seizures (postpartum), sleep requirement decreased, sluggishness, status epilepticus (postpartum), stroke (postpartum), sudden onset of sleep, tachycardia, tinnitus, urinary frequency, urinary incontinence, urinary retention, vasovagal attack, ventricular tachycardia, vertigo, visual disturbance
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); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (weak), CYP3A4 (weak)
Drug Interactions
Alcohol (Ethyl): May enhance the adverse/toxic effect of Bromocriptine. Bromocriptine may enhance the adverse/toxic effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alpha-/Beta-Agonists: Ergot Derivatives may enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Risk X: Avoid combination
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
Alpha1-Agonists: Ergot Derivatives may enhance the hypertensive effect of Alpha1-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha1-Agonists. Risk X: Avoid combination
Antipsychotics: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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): Anti-Parkinson's Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotics (Typical). Antipsychotics (Typical) may enhance the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson's agents. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CycloSPORINE: Bromocriptine may increase the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): Bromocriptine may increase the serum concentration of CycloSPORINE (Systemic). 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
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Macrolide Antibiotics: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically leading the development of ergotism. Exceptions: Azithromycin; Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylphenidate: May enhance the adverse/toxic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Risk C: Monitor therapy
Nitroglycerin: Ergot Derivatives may diminish the vasodilatory effect of Nitroglycerin. This is of particular concern in patients being treated for angina. Nitroglycerin may increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Posaconazole: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Protease Inhibitors: May increase the serum concentration 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
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
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.
Storage
Store at or below 25°C (77°F).
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).
In the treatment of type 2 diabetes mellitus, the mechanism of action is unknown; however, bromocriptine is believed to affect circadian rhythms which are mediated, in part, by dopaminergic activity, and are believed to play a role in obesity and insulin resistance. It is postulated that bromocriptine (when administered during the morning and released into the systemic circulation in a rapid, ‘pulse-like' dose) may reset hypothalamic circadian activities which have been altered by obesity, thereby resulting in the reversal of insulin resistance and decreases in glucose production, without increasing serum insulin concentrations.
Pharmacodynamics/Kinetics
Onset of action: Parlodel®: Prolactin decreasing effect: 1-2 hours
Distribution: Vd: ~61L
Protein binding: 90% to 96% (primarily albumin)
Metabolism: Primarily hepatic via CYP3A; extensive first-pass biotransformation (Cycloset®: ~93%)
Bioavailability: Parlodel®: 28%; Cycloset®: 65% to 95%
Half-life elimination: Cycloset®: ~6 hours; Parlodel®: Biphasic: Terminal: 15 hours (range: 8-20 hours)
Time to peak, serum: Parlodel®: 1-3 hours; Cycloset®: 53 minutes
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:
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)
Parkinsonism: 1.25 mg twice daily, increased by 2.5 mg/day in 2- to 4-week intervals as needed (maximum: 100 mg/day)
Type 2 diabetes (Cycloset®): Initial: 0.8 mg once daily; may increase at weekly intervals in 0.8 mg increments as tolerated; usual dose: 1.6-4.8 mg/day (maximum: 4.8 mg/day)
Neuroleptic malignant syndrome (unlabeled use): 2.5 mg (orally or via gastric tube) every 8-12 hours, increased to a maximum of 45 mg/day, if needed; continue therapy until NMS is controlled, then taper slowly (Gortney, 2009; Strawn, 2007)
Dosing adjustment in hepatic impairment: No guidelines are available; however, adjustment may be necessary due to extensive hepatic metabolism.
Administration: Oral
Administer with food to decrease GI distress.
Cycloset®: Administer within 2 hours of waking in the morning.
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 (acromegaly) and prolactin levels; Hb A1c and serum glucose (type 2 diabetes)
Reference Range
Recommendations for glycemic control in adults with diabetes:
Hb A1c: <7%
Preprandial capillary plasma glucose: 70-130 mg/dL
Peak postprandial capillary blood glucose: <180 mg/dL
Dietary Considerations
Should be taken with food to decrease GI distress.
Patient Education
May be prescribed in conjunction with levodopa/carbidopa. 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. Take at the same time each day. Maintain adequate hydration, unless instructed to restrict fluid intake. Do not use alcohol. Urine or perspiration may appear darker. You may experience drowsiness (can be sudden onset), dizziness, confusion, vision changes, loss of impulse control (possibly manifested as pathological gambling, libido increases, and/or binge eating), orthostatic hypotension, constipation, nasal congestion, nausea, vomiting, loss of appetite, or stomach discomfort. 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.
Geriatric Considerations
No special considerations are recommended since drug is dosed to response; however, elderly patients may have concomitant diseases or drug therapy which may complicate therapy. Because newer, more specific dopamine agonists have fewer side effects, bromocriptine is rarely the drug of choice in Parkinson's disease.
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.
In clinical trials in the treatment of type 2 diabetes, Cycloset® resulted in a mean change of Hb A1c (%) from baseline of -0.1 when used as monotherapy, and a mean change from baseline of -0.1 to -0.4 when used in combination with sulfonylureas.
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.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 5 mg
Parlodel®: 5 mg
Tablet, oral: 2.5 mg
Cycloset®: 0.8 mg
Parlodel® SnapTabs®: 2.5 mg [scored]
Pricing: U.S. (www.drugstore.com)
Capsules (Bromocriptine Mesylate)
5 mg (30): $135.99
Capsules (Parlodel)
5 mg (30): $259.99
Tablets (Bromocriptine Mesylate)
2.5 mg (30): $64.99
Tablets (Cycloset)
0.8 mg (30): $67.99
Tablets (Parlodel)
2.5 mg (30): $165.99
References
American Diabetes Association, “Standards of Medical Care in Diabetes Mellitus -- 2012,” Diabetes Care, 2012, 35(Suppl ):11-63.
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.
Gaziano JM, Cincotta AH, O'Connor CM, et al, “Randomized Clinical Trial of Quick-Release Bromocriptine Among Patients With Type 2 Diabetes on Overall Safety and Cardiovascular Outcomes,” Diabetes Care, 2010, 33(7):1503-8.
Gortney JS, Fagan A, and Kissack JC, “Neuroleptic Malignant Syndrome Secondary to Quetiapine,” Ann Pharmacother, 2009, 43(4):785-91.
Handelsman Y, Mechanick JI, Blonde L, et al, “American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan,” Endocr Pract, 2011, 17(Suppl 2):1-53.
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.
Parkes D, “Drug Therapy: Bromocriptine,” N Engl J Med, 1979, 301(16):873-8.
Pijl H, Ohashi S, Matsuda M, et al, “Bromocriptine: A Novel Approach to the Treatment of Type 2 Diabetes,” Diabetes Care, 2000, 23(8):1154-61.
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 February 2012
Content last modified February 2012
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