What is cabergoline (dopamine agonist)?

What is Cabergoline?

Cabergoline is a long-acting dopamine receptor agonist with high specificity and affinity for dopamine D2 receptors, used primarily to treat hyperprolactinemia by directly inhibiting prolactin secretion from pituitary lactotrophs. 1

Mechanism of Action

• Cabergoline exerts direct inhibitory effects on prolactin secretion by binding to D2 receptors on pituitary lactotroph cells, mimicking the hypothalamic dopamine that normally suppresses prolactin release 1
• The drug demonstrates high receptor specificity, with low affinity for dopamine D1, α1- and α2-adrenergic, and 5-HT1- and 5-HT2-serotonin receptors 1
• Its molecular formula is C26H37N5O2 with a molecular weight of 451.62, and it is chemically classified as an ergoline derivative 1

Pharmacokinetic Properties

• Peak plasma levels of 30-70 pg/mL occur within 2-3 hours after oral administration 1
• The elimination half-life ranges from 63-69 hours, which accounts for its prolonged duration of action and allows for convenient twice-weekly dosing 1
• Steady-state levels with once-weekly dosing are expected to be 2-3 fold higher than after a single dose 1
• The drug undergoes extensive tissue distribution, with pituitary levels exceeding plasma by more than 100-fold and elimination from the pituitary occurring with a half-life of approximately 60 hours 1

Clinical Efficacy

• Cabergoline normalizes prolactin levels in 83% of patients with hyperprolactinemic amenorrhea, compared to 59% with bromocriptine, and restores ovulatory cycles in 72% versus 52% with bromocriptine 2, 3
• In patients with prolactinomas, cabergoline normalizes prolactin in 60-70% of patients, reduces tumor size in 80-88%, improves visual deficits, resolves delayed puberty, and eliminates headache 3
• Tumor shrinkage greater than 80% occurs in 61% of patients with macroprolactinomas after 12-24 months of treatment 4
• Visual field abnormalities normalize in 70% of affected patients 5

Standard Dosing

• The initial dose is 0.25 mg twice weekly, with gradual titration up to 2 mg/week for most patients 3, 6
• For resistant cases, doses can be increased to 3.5 mg/week, or up to 7 mg/week in exceptional circumstances 3
• Once prolactin control is achieved, the maintenance dose can often be reduced to 0.5 mg/week 5
• Patients with macroprolactinomas typically require higher doses (median 1.0 mg/week) compared to those with microprolactinomas or idiopathic hyperprolactinemia (median 0.5 mg/week) 5

Safety Profile and Tolerability

• Cabergoline has a significantly better side effect profile than bromocriptine, with 52% versus 72% experiencing adverse events 3, 2
• Only 3% of patients discontinue cabergoline due to side effects, compared to 12% with bromocriptine 2
• Gastrointestinal symptoms (nausea, vomiting) are less frequent, less severe, and shorter-lived with cabergoline 2, 7
• Small nocturnal dose increments can reduce gastrointestinal intolerance and postural hypotension 3

Critical Safety Warnings

• For patients on doses >2 mg/week, annual echocardiography with cardiac auscultation is mandatory due to risk of cardiac valvulopathy 1, 6
• For patients on ≤2 mg/week, echocardiographic surveillance can be reduced to every 5 years 3, 6
• Cabergoline is contraindicated in patients with pre-existing cardiac or extracardiac fibrotic disorders 1
• Postmarketing cases of pleural, pericardial, and retroperitoneal fibrosis have been reported 1
• Psychological side effects (mood changes, depression, aggression, hypersexuality, impulse control disorders) are dose-independent and may be more common in children and adolescents 3

Important Clinical Caveats

• Tumor shrinkage in prolactinomas invading the sphenoid bone can cause cerebrospinal fluid leak (rhinorrhea), requiring urgent intervention including lumbar drain or surgical repair 3
• Dopamine agonists should not be used in pregnancy-induced hypertension (preeclampsia, eclampsia, postpartum hypertension) unless benefits outweigh risks 1
• The drug is extensively distributed in breast milk, suggesting potential exposure to nursing infants 1
• Treatment resistance is defined as failure to achieve normal prolactin levels and/or less than 50% tumor reduction after 3-6 months of maximally tolerated doses (at least 2 mg/week) 3