What is Bromocriptine (dopamine agonist) used for and what are its dosing recommendations?

Bromocriptine: Clinical Uses and Dosing

Primary Therapeutic Indications

Bromocriptine is a dopamine D2 receptor agonist primarily used for hyperprolactinemic conditions (including prolactinomas), Parkinson's disease, acromegaly, and peripartum cardiomyopathy, though cabergoline has largely replaced it as first-line therapy for prolactinomas due to superior efficacy and tolerability. 1, 2

Hyperprolactinemic Conditions and Prolactinomas

• Initial dosing: Start with 1.25-2.5 mg daily with food, increasing by 2.5 mg every 2-7 days as tolerated until optimal response is achieved 3
• Therapeutic range: 2.5-15 mg daily in adults; 2.5-10 mg daily in children aged 11-15 years with prolactin-secreting adenomas 3
• Efficacy: Bromocriptine suppresses prolactin secretion in approximately 90% of patients, restores gonadal function and fertility, and decreases prolactinoma size 4, 5
• Important caveat: Cabergoline is now preferred over bromocriptine due to better efficacy (83% vs 59% prolactin normalization) and significantly fewer adverse events (52% vs 72%) 1, 2

Acromegaly

• Initial dosing: Start with 1.25-2.5 mg at bedtime with food for 3 days 3
• Dose escalation: Add 1.25-2.5 mg every 3-7 days as tolerated 3
• Therapeutic range: 20-30 mg daily for most patients; maximum 100 mg daily 3
• Efficacy: Clinical improvement occurs in approximately 75% of patients, with growth hormone normalization in only 22% 5
• Monitoring: Assess growth hormone levels monthly; if no significant reduction occurs after a brief trial, consider dosage adjustment or discontinuation 3
• Role: Most useful as adjunctive therapy to surgery and/or radiotherapy rather than primary treatment 6

Parkinson's Disease

• Initial dosing: Start with 1.25 mg twice daily with meals 3
• Dose escalation: Increase by 2.5 mg every 14-28 days as needed 3
• Therapeutic approach: Low-dose therapy (5-30 mg/day) is effective in mild-to-moderate disease with minimal side effects; higher doses (31-100 mg/day) may be needed in advanced disease 7
• Combination therapy: Bromocriptine combined with levodopa is usually more effective than bromocriptine alone, with 71% improvement at low doses (23 mg/day average) and 58% at high doses (48 mg/day average) 7
• Maximum dose: Safety not established beyond 100 mg daily 3

Peripartum Cardiomyopathy (PPCM)

• Indication: Consider for severe acute heart failure with left ventricular ejection fraction <35% 2
• BOARD protocol dosing: 2.5 mg twice daily for 2 weeks, followed by 2.5 mg daily for 4 weeks 2
• Efficacy: One pilot study showed LVEF recovery from 27% to 58% at 6 months versus 27% to 36% with standard treatment (P=0.012) 2
• Critical safety requirement: Mandatory anticoagulation in all PPCM patients receiving bromocriptine due to reports of myocardial infarction 2

Administration Guidelines

• Always administer with food to reduce gastrointestinal side effects 3
• Nocturnal dosing can minimize gastrointestinal intolerance and postural hypotension 1
• Slow titration is essential to determine the lowest effective dose and minimize adverse effects 3

Adverse Effects and Monitoring

Common Side Effects

• Gastrointestinal: Nausea, vomiting (most common) 2, 8
• Cardiovascular: Postural hypotension, particularly during dose escalation 1, 2
• Psychological: Mood changes, depression, aggression, hypersexuality, impulse control disorders (dose-independent, may be more common in children and adolescents) 1, 2
• Vascular: Digital vasospasm and gastrointestinal bleeding at higher doses 5

Cardiac Monitoring for Prolactinoma Treatment

• While guidelines primarily address cabergoline, similar principles apply to high-dose bromocriptine therapy 9
• Baseline echocardiogram before initiating therapy 9
• Annual echocardiography for doses >2 mg/week (extrapolated from cabergoline data) 9
• Every 5 years for doses ≤2 mg/week 9

Special Populations

• Pregnancy: No evidence of increased abortion rates or congenital malformations in over 1,400 women exposed during early pregnancy 2
• Contraception during treatment: Use mechanical contraception until normal ovulatory cycles restored; discontinue bromocriptine if menstruation delayed >3 days beyond expected date and perform pregnancy test 3
• Chronic kidney disease: Use with caution due to lack of safety studies 2

Treatment Duration and Withdrawal

• Prolactinomas: Consider withdrawal after 2+ years if prolactin normalizes and no visible tumor remains 2
• Acromegaly with pituitary irradiation: Withdraw annually for 4-8 weeks to assess radiation effects and disease activity 3
• Important caveat: Withdrawal typically results in return of hyperprolactinemia, excess growth hormone secretion, or Parkinson's disease exacerbation 4

Treatment Resistance and Alternatives

• Definition of resistance: Failure to achieve normal prolactin levels and/or <50% tumor reduction after 3-6 months at maximally tolerated doses (at least 2 mg/week) 1
• Surgical intervention: Consider if vision deteriorates or fails to improve on medical therapy, or if dopamine agonist resistance, escape, or intolerance occurs 9
• Radiotherapy: Reserved for exceptional cases with growing prolactinomas where other modalities exhausted; achieves 93% tumor control but primarily used after surgical failure 1

Critical Safety Warning

• CSF leak risk: Watch for rhinorrhea in prolactinomas invading sphenoid bone, which can occur after tumor shrinkage with dopamine agonists and may require urgent intervention including lumbar drain or surgical repair 1

Long-Term Safety Profile

• Long-term bromocriptine treatment has minimal or no harmful effects on renal, hepatic, cardiac, or hematologic functions 8
• Overall represents an effective and safe option with high efficacy for multiple conditions when used appropriately 8