How do I initiate and titrate bromocriptine in an adult with a prolactinoma?

How to Initiate Bromocriptine for Prolactinoma

Critical First Principle: Cabergoline is Superior

Bromocriptine should not be your first-line dopamine agonist for prolactinoma—cabergoline is the preferred agent due to superior efficacy (83% vs 59% prolactin normalization), better tolerability (52% vs 72% adverse events), and more convenient dosing. 1

However, if bromocriptine is specifically required (due to cost, availability, or cabergoline intolerance), here is the evidence-based approach:

Starting Bromocriptine: Dosing Protocol

Initial Dosing Strategy

• Start with 1.25 mg (half of a 2.5 mg tablet) taken at bedtime with food 2
• The evening administration with food minimizes the most common initial adverse effects: nausea, vomiting, and postural hypotension 2
• This low starting dose allows tolerance to develop gradually 2

Titration Schedule

• Increase by 1.25 mg every 3-7 days as tolerated 2
• Target maintenance dose is typically 2.5 mg twice daily (total 5 mg/day) for microprolactinomas 2
• For macroprolactinomas, doses may need to reach 7.5-15 mg/day divided into 2-3 doses 2
• Some patients require individualized dosing based on prolactin response and tolerability 2

Alternative Dosing Approach

• Once-daily evening dosing has been shown equally effective to divided doses and may improve compliance 2
• This approach maintains efficacy while potentially reducing daytime side effects 2

Monitoring During Initiation

Biochemical Monitoring

• Check prolactin levels after 3-6 weeks at each stable dose to assess response 3
• Continue titration until prolactin normalizes or maximum tolerated dose is reached 2
• Once stable, monitor prolactin every 3-6 months 3

Radiological Monitoring

• For macroprolactinomas, obtain MRI at 3-6 months after starting therapy to assess tumor shrinkage 3
• Tumor shrinkage occurs in the majority of responsive macroprolactinomas 4, 5
• Close follow-up with imaging is essential as rare cases of disease progression during therapy have been reported 2

Managing Common Adverse Effects

Gastrointestinal and Cardiovascular Effects

• Nausea, vomiting, and postural hypotension are most common initially but typically resolve within days to weeks 2
• If intolerable, slow the titration further or temporarily reduce the dose 2
• Taking medication with food and at bedtime significantly reduces these effects 2

Dose-Independent Psychiatric Effects

• Watch for mood changes, depression, aggression, hypersexuality, and impulse control disorders at any dose 6, 1
• These dopaminergic effects occur independent of dose and are similar between bromocriptine and cabergoline 6
• May be more frequent in younger patients 6

Serious Complications to Monitor

• For invasive macroadenomas (especially those invading sphenoid bone), watch for rhinorrhea indicating cerebrospinal fluid leak 6
• This can occur within days to months (mean 3.3 months) as tumor shrinks 6
• Confirm with β2-transferrin or β-trace protein testing of nasal secretions 6
• May require urgent intervention including lumbar drain or surgical repair 6

When Bromocriptine Fails

Defining Resistance

• Resistance = failure to normalize prolactin AND/OR <50% tumor area reduction after 3-6 months at maximally tolerated doses (at least equivalent to 2 mg/week cabergoline, roughly 15 mg/day bromocriptine) 6, 2
• Resistance correlates directly with tumor size and baseline prolactin levels 6

Next Steps for Resistant Cases

• Switch to cabergoline if not already tried—it is more effective than bromocriptine 1, 4
• Cabergoline can be titrated up to 3.5 mg/week (or exceptionally 7 mg/week) for resistant cases 6, 1
• If dopamine agonist resistance persists, consider transsphenoidal surgery 6
• Radiotherapy is reserved for cases where surgery is not an option 6

Special Considerations for Pregnancy

• For microprolactinomas, discontinue bromocriptine once pregnancy is confirmed as risk of tumor enlargement is low 2
• For macroprolactinomas, treat with bromocriptine until significant tumor shrinkage occurs before attempting pregnancy, then discontinue once pregnancy confirmed 2
• Restart bromocriptine if symptomatic tumor enlargement occurs during pregnancy 2

Key Clinical Pitfalls

• Do not assume elevated prolactin always means prolactinoma—stalk compression from non-functional tumors can cause modest prolactin elevation (80-115 ng/mL) 5
• These non-prolactin-secreting tumors will not shrink with bromocriptine despite elevated prolactin 5
• Prolactin levels >100-200 ng/mL strongly suggest true prolactinoma 2
• Always confirm with imaging and consider pathological confirmation if surgery is performed 5