Pharmacologic Category

Anti-Parkinson Agent, Dopamine Agonist; Antidiabetic Agent, Dopamine Agonist; Ergot Derivative

Dosing: Adult

Diabetes mellitus, type 2 (Cycloset only): Oral: Note: Agents other than bromocriptine are recommended for treatment of patients with type 2 diabetes mellitus (ADA 2020).

Initial: 0.8 mg once daily in the morning; may increase at weekly intervals in 0.8 mg increments as tolerated; usual dose: 1.6 to 4.8 mg once daily (maximum: 4.8 mg/day).

Hyperprolactinemia: Oral: Initial: 1.25 to 2.5 mg daily; may be increased by 2.5 mg daily as tolerated every 2 to 7 days until optimal response (range: 2.5 to 15 mg/day).

Parkinsonism: Oral: 1.25 mg twice daily, increased by 2.5 mg daily in 2- to 4-week intervals as needed (maximum: 100 mg/day).

Neuroleptic malignant syndrome (off-label use): Oral: 2.5 mg (orally or via gastric tube) every 8 to 12 hours, increased to a maximum of 45 mg daily, if needed; continue therapy until NMS is controlled, then taper slowly (Gortney 2009; Strawn 2007).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. However, adjustment may be necessary due to extensive hepatic metabolism; use with caution.

Dosing: Pediatric

Hyperprolactinemia secondary to pituitary adenoma:

Children and Adolescents <16 years: Limited data available in age <11 years: Oral: Initial: 1.25 to 2.5 mg daily; dosage may be increased as tolerated to achieve a therapeutic response; usual effective range: 5 to 7.5 mg/day in divided doses; maximum daily dose: 10 mg/day (Fideleff 2009; Gillam 2004)

Adolescents ≥16 years: Oral: Initial: 1.25 to 2.5 mg daily; may be increased by 2.5 mg daily as tolerated every 2 to 7 days until optimal response; usual effective range: 5 to 7.5 mg/day in divided doses; maximum daily dose: 15 mg/day (Fideleff 2009; Gillam 2004)

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; however, adjustment may be necessary due to extensive metabolism; use with caution.

Use: Labeled Indications

Diabetes mellitus, type 2 (Cycloset only): To improve glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise

Hyperprolactinemia (excluding Cycloset): Treatment of prolactin-secreting pituitary adenoma or disorders associated with hyperprolactinemia including amenorrhea with or without galactorrhea, hypogonadism, or infertility

Parkinson disease (excluding Cycloset): Treatment of the signs and symptoms of idiopathic or postencephalitic Parkinson disease; as adjunctive treatment to levodopa (alone or with a peripheral decarboxylase inhibitor)

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Neuroleptic malignant syndrome Level of Evidence [C]

Data from a limited number of patients studied (case reports) suggest that bromocriptine may be beneficial for the treatment of neuroleptic malignant syndrome Ref. Additional data may be necessary to further define the role of bromocriptine in this condition.

Level of Evidence Definitions

Level of Evidence Scale

Use: Unsupported: Adult

Acromegaly

Although included as an FDA-approved use in the manufacturer's prescribing information for the treatment of acromegaly, clinical practice guidelines no longer suggest the use of bromocriptine for this indication due to limited efficacy compared to other available treatments (AACE [Katznelson 2011], ACG [Melmed 2018], ES [Katznelson 2014]).

Clinical Practice Guidelines

Diabetes:

AACE/ACE, “Consensus Statement on the Comprehensive Type 2 Diabetes Management Algorithm - 2020 Executive Summary,” January 2020

ADA, “Standards of Medical Care in Diabetes - 2020,” January 2020

Parkinson Disease:

Canadian Neurological Sciences Federation, “Canadian Guidelines on Parkinson's Disease,” 2012

Administration: Oral

Administer with food to decrease GI distress.

Cycloset: Administer within 2 hours of waking in the morning. If the morning dose is missed, wait until the next morning and resume with the usual dose.

Administration: Pediatric

Oral: May be taken with food to decrease GI distress

Dietary Considerations

Administer with food to decrease GI distress.

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F).

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat acromegaly.

• It is used to treat high prolactin levels.

• It is used to treat Parkinson's disease.

• It is used to treat some prolactin-secreting tumors.

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

• It may be given for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Upset stomach

• Throwing up

• Constipation

• Feeling sleepy, tired, or weak

• Trouble sleeping

• Stuffy nose

• Runny nose

• Diarrhea

• Not hungry

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Low blood sugar like dizziness, headache, feeling tired, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating

• Severe dizziness

• Passing out

• Vision changes

• Mood changes

• Behavioral changes

• Chest pain

• Trouble controlling body movements that is new or worse

• Severe headache

• Shortness of breath

• Excessive weight gain

• Swelling of arms or legs

• Strong urges that are hard to control like eating, gambling, sex, or spending money

• Falling asleep during activities such as eating or talking

• Back pain

• Black, tarry, or bloody stools

• Seizures

• Throwing up blood

• Severe stomach pain

• Sensing things that seem real but are not

• Unable to pass urine

• Change in amount of urine passed

• Confusion

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Hypersensitivity to bromocriptine, ergot alkaloids, or any component of the formulation

Additional product-specific contraindications:

Cycloset: Syncopal migraine; breast-feeding

Parlodel: Uncontrolled hypertension; pregnancy (risk to benefit evaluation must be performed in women who become pregnant during treatment for acromegaly, prolactinoma, or Parkinson 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)

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: Hypotension, including orthostatic hypotension and syncope, may occur, particularly upon initiation of therapy and dose escalation. In addition, hypertension, seizures, MI, and stroke have been reported. 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). Discontinue therapy and evaluate promptly if hypertension, severe, progressive, or unremitting headache (with or without visual disturbance), or evidence of CNS toxicity develops. In a scientific statement from the American Heart Association, bromocriptine has been determined to be an agent that may cause direct myocardial toxicity (magnitude: major) (AHA [Page 2016]).

• CNS depression: May cause CNS depression, which may impair physical or mental abilities, and episodes of sudden sleep onset particularly in patients with Parkinson disease; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Consider dosage reduction or discontinuation of therapy if symptoms occur.

• Hallucinations: Visual or auditory hallucinations may occur when administered alone or concomitantly with levodopa; dose reductions or discontinuation may be necessary. Symptoms may persist for several weeks following discontinuation.

• Impulse control disorders: Dopamine agonists used for Parkinson disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as new or increased gambling urges, sexual urges, uncontrolled spending, or other intense urges. Dose reduction or discontinuation of therapy reverses these behaviors in some, but not all cases.

• Melanoma: Risk for melanoma development is increased in Parkinson disease patients; drug causation or factors contributing to risk have not been established. Monitor all patients closely for melanoma and perform periodic skin examinations.

• Pleural/retroperitoneal fibrosis: Cases of pleural and pericardial effusions, as well as pleural, pulmonary, and/or retroperitoneal fibrosis and constrictive pericarditis have been reported with prolonged and high-dose daily use. Discontinue therapy if fibrotic changes are suspected.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (myocardial infarction; residual atrial, nodal, or ventricular arrhythmia).

• Dementia: Use with caution in patients with dementia; high doses may be associated with confusion and mental disturbances.

• Galactose intolerance/malabsorption (Parlodel): Avoid use in patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment may be necessary due to extensive hepatic metabolism.

• Macroadenomas: Discontinuation of therapy in patients with macroadenomas has been associated with rapid regrowth of tumor and increased prolactin serum levels.

• Peptic ulcer disease: Use with caution in patients with peptic ulcer disease; severe gastrointestinal bleeding has been reported (some fatal).

• Prolactin-secreting adenomas: Cerebrospinal fluid rhinorrhea has been observed in some of these patients.

• Psychosis: Use with caution in patients with psychosis; dopamine agonists may exacerbate the disorder or diminish the effectiveness of drugs used to treat the disorder. Use in patients with severe psychotic disorder is not recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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:

• Appropriate use (Cycloset): Not indicated for use in type 1 diabetes mellitus or diabetic ketoacidosis.

• Discontinuation of therapy: Dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on abrupt withdrawal or significant dosage reduction after long-term use; gradual dosage reduction is recommended when discontinuing therapy.

• 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.

* See Cautions in AHFS Essentials for additional information.

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 more dopamine-specific agonists have fewer side effects, bromocriptine is rarely the drug of choice in Parkinson's disease.

Type 2 diabetes: Intensive glucose control (HbA1c <6.5%) has been linked to increased all-cause and cardiovascular mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How "tightly" to control a geriatric patient's blood glucose needs to be individualized. Such a decision should be based on several factors, including the patient's functional and cognitive status, how well he/she recognizes hypoglycemic or hyperglycemic symptoms, and how well he/she responds to them and other disease states. An HbA1c <7.5% is an acceptable endpoint for a healthy older adult, while <8% is acceptable for frail elderly patients, those with a duration of illness >10 years, or those with comorbid conditions and requiring combination diabetes medications. For elderly patients with diabetes who are relatively healthy, attaining target goals for aspirin use, blood pressure, lipids, smoking cessation, and diet and exercise may be more important than normalized glycemic control.

Reproductive Considerations

Women with hyperprolactinemia may be infertile, have amenorrhea and galactorrhea. A mechanical contraceptive should be used during therapy until normal ovulatory menses is established. Contraception can then be discontinued if pregnancy is desired.

During treatment with bromocriptine, fertility may occur prior to restoration of menses in infertile women, therefore a pregnancy test is recommended every 4 weeks during the amenorrheic period. Once menses resume, pregnancy tests should be done any time a menstrual period is missed. Women not seeking pregnancy should be advised to use appropriate contraception.

Pregnancy Risk Factor

B

Pregnancy Considerations

Bromocriptine crosses the placenta (Molitch 2015). 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.

Bromocriptine should be discontinued if pregnancy is confirmed unless needed for treatment of a rapidly expanding macroadenoma. When used for the treatment of acromegaly or Parkinson disease, consider discontinuing therapy during pregnancy. If treatment is withdrawn, monitor for signs and symptoms of an enlarging prolactin secreting tumor. Regardless of indication, if bromocriptine is needed in a pregnant woman, monitor closely for hypertensive disorders during pregnancy and immediately postpartum.

Breast-Feeding Considerations

Use is contraindicated in nursing women when used for the treatment of type 2 diabetes and in postpartum women with a history of coronary artery disease or other severe cardiovascular conditions (unless withdrawal of medication is medically contraindicated).

Bromocriptine is known to inhibit lactation. 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.

Briggs' Drugs in Pregnancy & Lactation

• Bromocriptine

Adverse Reactions

Note: Frequency of adverse effects may vary by dose and/or indication.

>10%:

Gastrointestinal: Constipation (11% to 14%), nausea (18% to 33%)

Nervous system: Dizziness (≤13%), headache (≤13%)

Neuromuscular & skeletal: Asthenia (13%)

Respiratory: Rhinitis (14%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (6%), Raynaud's disease (<2%), syncope (<2%), vasospasm (digital: 3%)

Endocrine & metabolic: Hypoglycemia (4%)

Gastrointestinal: Abdominal cramps, abdominal distress, anorexia (4% to 5%), diarrhea (9%), dyspepsia (4% to 8%), gastrointestinal hemorrhage (<2%), vomiting (2% to 6%), xerostomia (≤4%)

Infection: Infection (6%)

Nervous system: Drowsiness (3%)

Ophthalmic: Amblyopia (8%)

Respiratory: Nasal congestion (≤4%), sinusitis (10%)

<1%:

Cardiovascular: Bradycardia, cardiac arrhythmia, vasodepressor syncope, ventricular tachycardia

Dermatologic: Alopecia, pallor

Nervous system: Cold intolerance, delusion, heavy headedness, insomnia, lassitude, lethargy, paranoid ideation, paresthesia, sleep disorder, tingling of the ears, visual hallucination

Neuromuscular & skeletal: Muscle cramps

Respiratory: Dyspnea

Frequency not defined:

Cardiovascular: Erythromelalgia, hypotension

Dermatologic: Skin mottling, skin rash

Genitourinary: Urinary frequency, urinary incontinence, urinary retention

Nervous system: Ataxia, auditory hallucination, confusion, depression, epileptiform seizure, fatigue, involuntary body movements, nervousness, nightmares, numbness, on-off phenomenon, sudden onset of sleep, vertigo

Ophthalmic: Blepharospasm, visual disturbance

Postmarketing:

Cardiovascular: Acquired valvular heart disease, cold extremity, constrictive pericarditis, pericardial effusion, pericarditis, peripheral edema, tachycardia

Dermatologic: Allergic skin reaction, pale extremities (fingers and toes)

Endocrine & metabolic: Increased libido

Gastrointestinal: Abdominal pain, dysphagia, gastrointestinal ulcer

Genitourinary: Retroperitoneal fibrosis

Nervous system: Anxiety, atypical sexual behavior, dyskinesia, impulsivity, neuroleptic malignant syndrome (syndrome-like symptoms), pathological gambling, psychomotor agitation, psychosis

Neuromuscular & skeletal: Dyskinesia, lower limb cramp

Ophthalmic: Blurred vision

Otic: Tinnitus

Respiratory: Pleural effusion, pleurisy, pleuropulmonary fibrosis, pulmonary fibrosis, rhinorrhea (cerebrospinal fluid, hyperprolactinemic indications)

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Ergot Alkaloid Allergy

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Alcohol (Ethyl): May enhance the adverse/toxic effect of Bromocriptine. Bromocriptine may enhance the adverse/toxic effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alizapride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

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

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

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Amisulpride (Injection): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Amisulpride (Oral): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride (Oral). Risk X: Avoid combination

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Exceptions: Danazol. Risk C: Monitor therapy

Antipsychotic Agents (First Generation [Typical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Management: Avoid concomitant therapy if possible. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Exceptions: Methotrimeprazine. Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Beta-Blockers: May enhance the vasoconstricting effect of Ergot Derivatives. Management: Avoid coadministration of beta-blockers and ergot derivatives whenever possible. If concomitant use cannot be avoided, monitor patients closely for evidence of excessive peripheral vasoconstriction. Risk D: Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Brivudine [INT]: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Specifically, the risk of chorea may be increased. Risk C: Monitor therapy

Bromopride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Risk X: Avoid combination

BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. Risk C: Monitor therapy

Chloroprocaine: May enhance the hypertensive effect of Ergot Derivatives. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Bromocriptine. Exceptions: Nefazodone. Risk X: Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Diethylstilbestrol: May enhance the adverse/toxic effect of Bromocriptine. Specifically, the risk for amenorrhea may be increased with the combination. Risk C: Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lisuride: May enhance the adverse/toxic effect of Ergot Derivatives. Risk X: Avoid combination

Lorcaserin (Withdrawn From US Market): May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin (Withdrawn From US Market) may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. Risk X: Avoid combination

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Macrolide Antibiotics: May increase the serum concentration of Ergot Derivatives. Cabergoline and Clarithromycin may interact, see specific monograph for full details. Exceptions: Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk X: Avoid combination

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Methotrimeprazine: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Methotrimeprazine. Risk X: Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nefazodone: Ergot Derivatives may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Protease Inhibitors: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

Reboxetine: May enhance the hypertensive effect of Ergot Derivatives. Risk C: Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Roxithromycin: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Serotonergic Agents (High Risk): Ergot Derivatives may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Nefazodone. Risk C: Monitor therapy

Serotonin 5-HT1D Receptor Agonists (Triptans): Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists (Triptans). Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Solriamfetol: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Somatostatin Analogs: May increase the serum concentration of Bromocriptine. Somatostatin Analogs may also delay bromocriptine absorption and time to maximum plasma concentrations. Risk C: Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Sulpiride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Genes of Interest

• Cytochrome P450 3A4

Monitoring Parameters

Blood pressure and heart rate (orthostatic vital signs; baseline and periodically thereafter); hepatic, renal, hematopoietic, and cardiovascular function (periodically); visual fields (prolactinoma; periodic); pregnancy test during amenorrheic period; prolactin levels; GI bleeding (patients with history of peptic ulcer); melanoma skin examinations (regular assessment)

Diabetes mellitus, type 2: Serum glucose and HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2020])

Reference Range

Recommendations for glycemic control in patients with diabetes:

Nonpregnant adults with diabetes (ADA 2020):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics).

Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).

Peak postprandial capillary blood glucose: <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).

Older adults (≥65 years of age) (ADA 2020):

Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (eg, sulfonylureas) (LeRoith 2019).

HbA1c: <7.5% (healthy); <8% (complex/intermediate health); <8.5% (very complex/poor health) (individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment).

Preprandial capillary blood glucose: 90 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).

Bedtime capillary blood glucose: 90 to 150 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).

Classification of hypoglycemia (ADA 2020):

Level 1: ≥54 to ≤70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.

Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.

Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.

Advanced Practitioners Physical Assessment/Monitoring

Monitor blood pressure at beginning of therapy and periodically during course of treatment.

Nursing Physical Assessment/Monitoring

Monitor blood pressure at beginning of therapy and periodically during course of treatment.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Parlodel: 5 mg

Generic: 5 mg

Tablet, Oral:

Cycloset: 0.8 mg

Parlodel: 2.5 mg [scored]

Generic: 2.5 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Generic: 5 mg

Tablet, Oral:

Generic: 2.5 mg

Anatomic Therapeutic Chemical (ATC) Classification

• G02CB01
• N04BC01

Generic Available (US)

Yes

Pricing: US

Capsules (Bromocriptine Mesylate Oral)

5 mg (per each): $9.31

Capsules (Parlodel Oral)

5 mg (per each): $11.76

Tablets (Bromocriptine Mesylate Oral)

2.5 mg (per each): $4.14 - $6.27

Tablets (Cycloset Oral)

0.8 mg (per each): $5.33

Tablets (Parlodel Oral)

2.5 mg (per each): $7.32

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Semisynthetic ergot alkaloid derivative and a sympatholytic dopamine D2 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 (Gaziano 2010; Pijl 2000).

Pharmacodynamics/Kinetics

Distribution: Vd: ~61L

Protein binding: 90% to 96% (primarily albumin)

Metabolism: Primarily hepatic via CYP3A; extensive first-pass biotransformation (Cycloset: ~93%)

Bioavailability: Cycloset: 65% to 95%

Half-life elimination: Cycloset: ~6 hours; Parlodel: 4.85 hours

Time to peak, serum: Cycloset: 53 minutes; Parlodel: 2.5 ± 2 hours

Excretion: Feces (~82%); urine (2% to 6%)

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: Plasma levels may increase with hepatic impairment.

Local Anesthetic/Vasoconstrictor Precautions

Bromocriptine is a semisynthetic ergot alkaloid derivative; there is a possibility that it has vasoconstricting effects; use vasoconstrictor with caution

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Patients may experience orthostatic hypotension as they stand up after treatment; especially if lying in dental chair for extended periods of time. Use caution with sudden changes in position during and after dental treatment.

Effects on Bleeding

No information available to require special precautions

Related Information

• Oral Antidiabetic Agents Comparison Table

Pharmacotherapy Pearls

Usually used with levodopa or levodopa/carbidopa to treat Parkinson 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 HbA1c (%) 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.

Index Terms

Bromocriptine Mesylate; Cycloset

FDA Approval Date

June 28, 1978

References

American Diabetes Association (ADA). 6. Glycemic Targets. Diabetes Care. 2017;40(Suppl 1):S48-S56.[PubMed 27979893]

American Diabetes Association (ADA). Standards of Medical Care in Diabetes–2020. Diabetes Care. 2020;43(suppl 1):S1-S212. https://care.diabetesjournals.org/content/43/Supplement_1. Accessed January 22, 2020.

Bromocriptine [prescribing information]. Columbus, OH; American Health Packaging; no date.

Cycloset (bromocriptine mesylate) [prescribing information]. Tiverton, RI: VeroScience LLC; April 2020.

Cycloset (bromocriptine mesylate) [prescribing information]. Tiverton, RI: VeroScience LLC; February 2020.

Factor SA, “Current Status of Symptomatic Medical Therapy in Parkinson’s Disease,” Neurotherapeutics, 2008, 5(2):164-80.[PubMed 18394561]

Fideleff HL, Boquete HR, Suárez MG, Azaretzky M. Prolactinoma in children and adolescents. Horm Res. 2009;72(4):197-205.[PubMed 19786791]

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.[PubMed 20332352]

Gillam MP, Fideleff H, Boquete HR, et al, “Prolactin Excess: Treatment and Toxicity,” Pediatr Endocrinol Rev, 2004, 2(suppl)1:108-14.[PubMed 16456489]

Gortney JS, Fagan A, and Kissack JC, “Neuroleptic Malignant Syndrome Secondary to Quetiapine,” Ann Pharmacother, 2009, 43(4):785-91.[PubMed 19299325]

Katznelson L, Atkinson JL, Cook DM, Ezzat SZ, Hamrahian AH, Miller KK; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly--2011 update. Endocr Pract. 2011;17(suppl 4):1-44.[PubMed 21846616]

Katznelson L, Laws ER Jr, Melmed S, et al; Endocrine Society. Acromegaly: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. doi: 10.1210/jc.2014-2700.[PubMed 25356808]

LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi: 10.1210/jc.2019-00198.[PubMed 30903688]

Melmed S, Bronstein MD, Chanson P, et al. A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561.[PubMed 30050156]

Molitch ME. Endocrinology in pregnancy: management of the pregnant patient with a prolactinoma. Eur J Endocrinol. 2015;172(5):R205-R213. doi: 10.1530/EJE-14-0848.[PubMed 25805896]

Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association [published correction appears in Circulation. 2016;134(12):e261]. Circulation. 2016;134(6):e32-e69. doi: 10.1161/CIR.0000000000000426.[PubMed 27400984]

Parlodel SnapTabs and Capsules (bromocriptine mesylate) [prescribing information]. Parsippany, NJ: Validus Pharmaceuticals LLC; May 2018.

Parlodel SnapTabs and Capsules (bromocriptine mesylate) [prescribing information]. Parsippany, NJ: Validus Pharmaceuticals LLC; December 2019.

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.[PubMed 10937514]

Rosenberg MR, Green M. Neuroleptic malignant syndrome. Review of response to therapy. Arch Intern Med. 1989;149(9):1927-1931.[PubMed 2673115]

Strawn JR, Keck PE Jr, and Caroff SN, "Neuroleptic Malignant Syndrome," Am J Psychiatry, 2007, 164(6):870-6.[PubMed 17541044]

Brand Names: International

Antiprotin (AE); Barlolin (TW); Brameston (BM, BS, BZ, EC, GY, JM, MT, PR, SG, SR, TT); Brom (LK); Bromergon (BD, HR, TH); Bromo-Kin (FR); Bromocorn (PL); Bromocriptin-Richter (HU); Bromocriptina (CO); Bromolac (BD); Butin (TW); Cripsa (ID); Criptine (BD); Criten (CL); Demil (TW); Deprolac (TW); Dopagon (EG); Gynodel (TR); Kripton (AU); Lactodel (EG); Medocripsine (LK); Medocriptine (BG, CZ, HK); Parlodel (AE, AR, AU, BB, BD, BE, BF, BH, BJ, BR, CH, CI, CL, CN, CO, CY, CZ, DK, EC, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HK, HN, HR, HU, ID, IE, IN, IQ, IR, IT, JO, JP, KE, KR, KW, LB, LR, LY, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NL, NO, NZ, OM, PE, PH, PK, PL, PT, PY, QA, RU, SA, SC, SD, SK, SL, SN, SY, TN, TR, TW, TZ, UA, UG, UY, VE, VN, YE, ZM); Pravidel (DE, SE); Protinal (IN); Ronalin (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Serocryptin (AE, BH, CY, HU, IQ, IR, IT, JO, KW, LB, LY, MY, OM, PE, QA, SA, SY, YE); Suplac (TH)

Last Updated 8/3/20