Health Canada's review of the available information has established a link between use of the dopamine agonists pramipexole, quinagolide, or ropinirole and the risk of dopamine agonist withdrawal syndrome (DAWS). DAWS may occur after reducing the dose of or discontinuing dopamine agonists, and includes symptoms such as apathy, anxiety, depression, fatigue, sweating, panic attacks, insomnia, irritability, and pain. The Canadian product information for pramipexole has been updated to include a warning on the risk of DAWS. Health Canada will work with the manufacturers of quinagolide and ropinirole to update the product information to include a warning on the risk of DAWS. At this time, there is not enough information to establish a link between other dopamine agonists that were assessed as part of this safety review (ie, apomorphine, bromocriptine, cabergoline, pergolide [no longer marketed], and rotigotine) and DAWS. As a precaution, Health Canada will work with the manufacturers of these dopamine agonists to include the potential risk of DAWS in the product information.
Further information is available at https://hpr-rps.hres.ca/reg-content/summary-safety-review-detail.php?lang=en&linkID=SSR00269.
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)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer’s labeling; however, adjustment may be necessary due to extensive metabolism; use with caution.
(For additional information see "Bromocriptine: Drug information")
Diabetes mellitus, type 2, treatment (alternative agent) (Cycloset only):
Note: Agents other than bromocriptine are recommended for treatment of patients with type 2 diabetes mellitus (ADA 2020).
Oral: Initial: 0.8 mg once daily in the morning. If additional glycemic control is needed, may increase dose in 0.8 mg increments at weekly intervals as tolerated; usual dose: 1.6 to 4.8 mg once daily (maximum: 4.8 mg/day).
Hyperprolactinemic disorders (alternative to cabergoline) (excluding Cycloset):
Oral: Initial: 1.25 to 2.5 mg once daily; may increase dose by 2.5 mg/day every 2 to 7 days as tolerated, if needed based on serum prolactin levels (range: 2.5 to 15 mg/day administered in 1 or 2 divided doses) (Sabuncu 2001; manufacturer's labeling). Note: In patients with persistently elevated serum prolactin levels despite maximally tolerated dosage, consider switching to cabergoline (ES [Melmed 2011]).
Duration of therapy: Treatment for ≥2 years has been recommended to reduce the risk of recurrence. Ensure that prolactin levels are normal and there is no visible tumor on MRI (in patients with prolactinoma) prior to tapering and discontinuing (ES [Melmed 2011]; Xia 2018).
Parkinson disease (alternative agent) (excluding Cycloset):
Note: Agents other than bromocriptine are recommended for treatment of patients with Parkinson disease (MDS [Fox 2018]).
Oral: 1.25 mg twice daily, increased by 2.5 mg daily in 2- to 4-week intervals as needed (maximum: 100 mg/day). Note: The European Medicines Agency has suggested a maximum dose of 30 mg/day to reduce the risk of cardiac fibrosis (EMA 2008).
Neuroleptic malignant syndrome, moderate to severe (adjunctive agent) (excluding Cycloset) (off-label use):
Note: Discontinue the causative agent(s) as soon as possible and provide aggressive supportive care throughout therapy (Strawn 2007; van Rensburg 2019).
Oral: Initial: 2.5 mg every 8 to 12 hours; may increase to a maximum of 45 mg/day if needed. Continue therapy for ≥10 days, then taper slowly (Gortney 2009; Strawn 2007; van Rensburg 2019).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling. However, adjustment may be necessary due to extensive hepatic metabolism; use with caution.
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
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 5 mg
Tablet, Oral:
Generic: 2.5 mg
Oral: May be taken with food to decrease GI distress
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.
In neuroleptic malignant syndrome, administration via nasogastric tube has been described (Gortney 2009; Strawn 2007; van Rensburg 2019).
Store at 20°C to 25°C (68°F to 77°F).
Treatment of dysfunctions associated with hyperprolactinemia, including amenorrhea with or without galactorrhea, infertility, or hypogonadism (FDA approved in adults); treatment of prolactin-secreting adenomas (FDA approved in ages ≥11 years and adults); treatment of acromegaly (FDA approved in adults); treatment of Parkinson disease (FDA approved in adults); treatment of type 2 diabetes mellitus as an adjunct to diet and exercise (Cycloset: FDA approved in adults); has also been used for neuroleptic malignant syndrome
Note: Although FDA approved, bromocriptine is not generally used in patients with type 2 diabetes but may be tried in specific situations (ADA 2017)
Bromocriptine may be confused with benztropine, brimonidine
Cycloset may be confused with Glyset
Parlodel may be confused with pindolol, Provera
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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)
Hypersensitivity to bromocriptine, ergot alkaloids, or any component of the formulation.
Additional product-specific contraindications:
Cycloset: Syncopal migraine; postpartum patients; lactating patients.
Parlodel: Uncontrolled hypertension; pregnancy (risk to benefit evaluation must be performed in patients who become pregnant during treatment - hypertension during treatment should generally result in efforts to withdraw); postpartum patients with a history of coronary artery disease or other severe cardiovascular conditions (unless withdrawal of medication is medically contraindicated).
Canadian labeling: Additional contraindications (not in US labeling): Uncontrolled hypertension of pregnancy; history of toxemia of pregnancy.
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). 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).
• Hallucinations: Visual or auditory hallucinations may occur when administered alone or concomitantly with levodopa; 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.
• 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.
• 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.
Special populations:
• Postpartum patients: Adverse events, such as hypertension, myocardial infarction, psychosis, seizures, and stroke have been reported in postpartum patients; these reactions can be severe and life threatening. Risk may be increased in patients with cardiovascular disease.
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. Apathy, anxiety, depression, fatigue, insomnia, pain, and sweating have occurred during taper or after discontinuation of therapy, which may not respond well to levodopa. Educate patient on potential of withdrawal symptoms; consider readministration of a dopamine agonist at the lowest effective dose in patients experiencing symptoms.
• Visual monitoring: Rapidly progressing visual field loss requires neurosurgical consultation.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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: Bromocriptine may enhance the hypertensive effect of Alpha-/Beta-Agonists. Management: Consider alternatives to this combination when possible. If combined, monitor for hypertension and tachycardia, and do not coadminister these agents for more than 10 days. Risk D: Consider therapy modification
Alpha1-Agonists: Bromocriptine may enhance the hypertensive effect of Alpha1-Agonists. Management: Consider alternatives to this combination when possible. If combined, monitor for hypertension and tachycardia, and do not coadminister these agents for more than 10 days. Risk D: Consider therapy modification
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 used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Injection): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Amisulpride (Oral): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride (Oral). Amisulpride (Oral) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Antipsychotic Agents (First Generation [Typical]): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). 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). 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
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Bortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic 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: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Bromocriptine. Risk C: Monitor therapy
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. Management: Consider alternatives to the use of bromocriptine with strong CYP3A4 inhibitors. If combined, monitor closely for increased bromocriptine toxicities and consider bromocriptine dose reductions. Risk D: Consider therapy modification
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
Domperidone: May diminish the therapeutic effect of Bromocriptine. 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
Ergot Derivatives: May enhance the adverse/toxic effect of Bromocriptine. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
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
Herbal Products with Blood Pressure Lowering Effects: 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
Kava Kava: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Kava Kava may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). 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
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: Bromocriptine may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Bromocriptine. Management: Consider alternatives to this combination. If combined, monitor for increased bromocriptine toxicities and consider bromocriptine dose reductions. Additionally, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
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
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
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
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Serotonin 5-HT1D Receptor Agonists (Triptans): Bromocriptine may enhance the adverse/toxic effect of Serotonin 5-HT1D Receptor Agonists (Triptans). Management: Consider alternatives to this combination when possible. If combined, monitor for increased bromocriptine and triptan toxicities. Risk D: Consider therapy modification
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
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
Administer with food to decrease GI distress.
Females with hyperprolactinemia may be infertile, have amenorrhea and galactorrhea. 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. A mechanical contraceptive should be used during therapy until normal ovulatory menses is established. Contraception can then be discontinued if pregnancy is desired.
Bromocriptine is approved for the treatment of prolactin-secreting pituitary adenomas (prolactinomas) and may be the preferred dopamine agonist for females planning a pregnancy due to its shorter half-life in comparison to other recommended agents. Early fetal exposure may occur prior to pregnancy detection (Glezer 2020).
Bromocriptine crosses the placenta (Endocrine Society [Melmed 2011]).
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 is approved for the treatment of prolactin-secreting pituitary adenomas (prolactinomas). Bromocriptine should be discontinued once pregnancy is confirmed unless needed for treatment of a rapidly expanding macroadenoma; treatment can be continued in patients with symptomatic growth. Monitoring of prolactin levels should be suspended during pregnancy (Endocrine Society [Melmed 2011]; Glezer 2020). If treatment is withdrawn, monitor for signs and symptoms of an enlarging prolactin secreting tumor.
The incidence of Parkinson disease in pregnancy is relatively rare. Information related to the use of bromocriptine in pregnant patients is limited for this indication and other agents may be preferred (Olivola 2020; Young 2020).
Bromocriptine has been evaluated for the adjunctive treatment of peripartum cardiomyopathy (ESC [Bauersachs 2016]), although use for this purpose remains controversial and additional studies may be needed (Sliwa 2017).
Regardless of indication, if bromocriptine is needed, monitor closely for hypertensive disorders during pregnancy and immediately postpartum.
Blood pressure and heart rate (orthostatic vital signs; baseline and periodically thereafter); hepatic, renal, hematopoietic, and cardiovascular function (periodically); visual field (prolactinoma; periodic); pregnancy test during amenorrheic period; growth hormone (acromegaly; periodic); prolactin levels; GI bleeding (patients with history of peptic ulcer); melanoma skin examinations (regular assessment); HbA1c and serum glucose (type 2 diabetes mellitus)
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).
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%)
Hepatic function impairment: Plasma levels may increase with hepatic impairment.
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): $6.21
Tablets (Parlodel Oral)
2.5 mg (per each): $7.32
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