How do I use bromocriptine (dopamine agonist) for medical treatment?

How to Use Bromocriptine

Primary Clinical Indications

Bromocriptine is primarily used for hyperprolactinemic conditions (including prolactinomas), acromegaly, Parkinson's disease, and as an adjunctive agent in type 2 diabetes mellitus, with dosing and administration varying significantly by indication. 1

Hyperprolactinemia and Prolactinomas

For hyperprolactinemic conditions, start with 1.25-2.5 mg daily at bedtime with food, increasing by 2.5 mg every 2-7 days as tolerated until achieving therapeutic response. 1

• The therapeutic dosage typically ranges from 2.5 to 15 mg daily in adults 1
• In children aged 11-15 years with prolactin-secreting adenomas, start with 1.25-2.5 mg daily, with therapeutic doses ranging from 2.5 to 10 mg daily 1
• Bromocriptine reduces prolactin levels to normal and restores sexual and reproductive function in approximately 90% of patients with hyperprolactinemia 2
• However, cabergoline is now preferred over bromocriptine for resistant hyperprolactinemia due to superior efficacy and tolerability 3, 4

Resistance and Dose Escalation

• For patients resistant to standard doses, graduated dose increments up to 3.5 mg per week of cabergoline (not bromocriptine) are recommended, or up to 7 mg per week in exceptional cases 3
• Resistance is defined as failure to achieve normal prolactin levels and less than 50% reduction in tumor area after 3-6 months of maximally tolerated dopamine agonist doses 3
• Small nocturnal dose increments effectively diminish gastrointestinal intolerance and postural hypotension 3

Acromegaly

For acromegaly, initiate therapy with 1.25-2.5 mg at bedtime with food for 3 days, then add 1.25-2.5 mg every 3-7 days until optimal benefit is achieved. 1

• The usual optimal therapeutic dosage ranges from 20 to 30 mg daily, with a maximum of 100 mg daily 1
• Bromocriptine produces subjective improvement in 75% of acromegalic patients, with growth hormone reduction to normal in 22% of cases 2
• Periodic assessment of circulating growth hormone levels serves as a guide for therapeutic potential 1
• If no significant growth hormone reduction occurs after a brief trial, reassess clinical features and consider dosage adjustment or discontinuation 1

Parkinson's Disease

For Parkinson's disease, start with 1.25 mg twice daily with meals, increasing by 2.5 mg every 14-28 days as tolerated while maintaining levodopa dosage. 1

• Assessments should occur at two-week intervals during titration to ensure the lowest effective dose 1
• When reducing levodopa due to adverse reactions, increase bromocriptine gradually in small 2.5 mg increments 1
• Safety has not been demonstrated at doses exceeding 100 mg daily 1

Type 2 Diabetes Mellitus

For diabetes, a quick-release formulation of bromocriptine (Cycloset) is administered at 0.8-4.8 mg daily in the early morning to reset circadian rhythms and improve insulin resistance. 5

• The American Diabetes Association recognizes bromocriptine as an option for specific situations in type 2 diabetes management 3
• Quick-release bromocriptine lowers HbA1c by 0.6-1.2% (7-13 mmol/mol) as monotherapy or in combination with other antidiabetes medications 5
• Doses used for diabetes are much lower than those for Parkinson's disease and have not been associated with retroperitoneal fibrosis or heart valve abnormalities 5

Peripartum Cardiomyopathy (Specialized Use)

For severe acute heart failure caused by peripartum cardiomyopathy with LVEF <35%, the "BOARD" protocol recommends 2.5 mg twice daily for 2 weeks, followed by 2.5 mg daily for 4 weeks. 6

• This indication requires obligatory anticoagulation due to reports of myocardial infarction associated with bromocriptine use 6
• One pilot study showed LVEF recovery from 27% to 58% at 6 months with bromocriptine versus 27% to 36% with standard treatment (P=0.012) 6

Critical Administration Guidelines

Timing and Food

• Always administer bromocriptine with food to reduce the high incidence of vomiting that occurs under fasting conditions 1
• For diabetes, timing is crucial—administer in the early morning for peak delivery to reset circadian rhythms 5

Dose Titration Principles

• Start at the lowest effective dose and increase slowly on an individual basis 1
• Frequent evaluation during dose escalation determines the lowest dosage producing therapeutic response 1
• The goal is to avoid exceeding the minimum effective dose while achieving optimal therapeutic benefit 1

Common Side Effects and Management

The most common side effects include gastrointestinal intolerance, postural hypotension, and psychological effects such as mood changes, depression, aggression, hypersexuality, and impulse control disorder. 3, 6

• Nausea is common but the drug is otherwise well tolerated at diabetes doses 5
• Dose-independent psychological intolerance occurs with similar frequency across all dopamine agonists 3
• In higher doses used for Parkinson's disease, digital vasospasm and gastrointestinal bleeding have occurred 2

Serious Adverse Events Requiring Monitoring

• Cerebrospinal fluid leak can occur during long-term treatment and may require urgent intervention (lumbar drain or surgical repair) with temporary cessation of therapy 3
• Detection of β2-transferrin or β-trace protein in nasal secretions confirms cerebrospinal fluid leak 3
• Apoplexy has been described during dopamine agonist therapy in both adults and children 3
• Echocardiography monitoring may be required for higher doses used in prolactinomas 6

Special Populations and Precautions

Pregnancy and Contraception

• For hyperprolactinemic patients desiring pregnancy, use mechanical contraception until normal ovulatory cycles are restored 1
• If menstruation does not occur within 3 days of the expected date after discontinuing contraception, stop bromocriptine and perform a pregnancy test 1
• No evidence of increased abortion rates or congenital malformations has been reported in over 1,400 women who took bromocriptine during early pregnancy 6

Renal Impairment

• Use bromocriptine with caution in chronic kidney disease due to lack of safety studies 6

Treatment Withdrawal

• For prolactinomas, withdrawal may be considered after 2+ years if prolactin levels normalize and no visible tumor remains 6
• Withdrawal of bromocriptine is associated with reversal of beneficial effects in most patients—return of hyperprolactinemia, excess growth hormone secretion, or exacerbation of Parkinson's disease 7
• After prolonged cabergoline treatment (not bromocriptine specifically), only 20-30% of patients experience return of hyperprolactinemia symptoms upon discontinuation 4

When Surgery or Alternative Therapy Is Indicated

Following multidisciplinary discussion, offer surgery for prolactinomas when patients are unable to tolerate or are resistant to high-dose dopamine agonists, or when vision deteriorates on medical therapy. 3

• Transsphenoidal surgery induces remission in 30-50% of adults with prolactinomas 3
• Residual post-operative hyperprolactinemia is typically more responsive to dopamine agonists than pre-operatively 3
• Radiotherapy should be offered if surgery is not an option 3

Pharmacokinetic Considerations

• Bromocriptine undergoes extensive first-pass metabolism with 90-96% protein binding to serum albumin 1
• CYP3A4 is the main metabolic pathway; inhibitors or potent substrates may increase bromocriptine levels 1
• About 82% of the dose is recovered in feces and 5.6% in urine 1
• Mean elimination half-life is approximately 4.85 hours 1