Makindo Medical Notes

Related Subjects: | Prolactin | Prolactinoma

⚠️ Key Safety Warning: Cabergoline is associated with fibrotic reactions — particularly cardiac valvulopathy, pleural, pericardial, and retroperitoneal fibrosis. 💡 Monitoring: Baseline and periodic echocardiogram, chest X-ray, ESR, U&Es are essential for long-term use. Always 🔗 check the BNF entry for up-to-date prescribing advice.

🧠 About

• Cabergoline is a potent, long-acting ergot-derived dopamine D₂ receptor agonist.
• Used in the treatment of hyperprolactinaemia (prolactinoma) and as adjunct therapy in Parkinson’s disease.
• Inhibits prolactin release from the anterior pituitary lactotroph cells, suppressing lactation and normalising menstrual cycles.
• Compared with bromocriptine, cabergoline has greater selectivity, longer half-life, and fewer gastrointestinal effects.

⚙️ Mode of Action

• Dopamine D₂ receptor agonist: mimics dopamine activity in the hypothalamus and pituitary.
• Suppresses prolactin secretion by inhibiting adenylate cyclase activity and reducing cAMP in lactotrophs.
• In Parkinson’s disease, stimulates striatal dopamine receptors to enhance dopaminergic transmission, improving motor symptoms.
• Ergot-derived structure explains its association with fibrotic complications (valvular and serosal).

💊 Indications & Typical Doses

• Parkinson’s Disease:
  • Start with 1 mg once daily, increasing by 500 mcg/week until symptom control (max 3 mg/day).
  • Always introduce gradually to reduce nausea and hypotension.
• Prolactinoma / Hyperprolactinaemia:
  • 500 mcg once per week, titrated up to 2 mg/week in divided doses as required.
• Postpartum Lactation Suppression:
  • To prevent lactation: 1 mg single dose on day 1 postpartum.
  • To suppress established lactation: 250 mcg twice daily for 2 days.

🧪 Pharmacology

• Class: Ergot-derived dopamine D₂ agonist.
• Half-life: ~65 hours (allows once or twice weekly dosing).
• Metabolism: hepatic (CYP3A4); excreted mainly in bile.
• Onset: Prolactin suppression within 3 hours; effect lasts 7–14 days.

🤝 Interactions

• Antipsychotics (especially typical agents) antagonise dopamine effects and reduce efficacy.
• Antihypertensives — additive hypotensive effect; monitor closely.
• Macrolide antibiotics (e.g., erythromycin) inhibit CYP3A4 and can raise cabergoline levels.
• See BNF for full list of drug interactions.

⚠️ Cautions

• Abrupt cessation can precipitate a neuroleptic malignant–like syndrome (rigidity, pyrexia, autonomic instability).
• Postural hypotension — advise slow position changes and caution when driving.
• Drowsiness or sudden sleep attacks may occur — particularly in Parkinson’s therapy.
• Acute porphyria and fibrotic risk require extra vigilance.
• Impulse control disorders (hypersexuality, gambling, compulsive shopping/eating) — monitor patients and carers.
• Baseline and annual cardiac echo, CXR, ESR, U&E when used chronically.

⛔ Contraindications

• History of pulmonary, pericardial, or retroperitoneal fibrosis.
• Valvular heart disease.
• Severe hepatic impairment.
• Uncontrolled hypertension or pre-eclampsia.
• See BNF for full contraindication list.

💢 Side Effects

• Common: nausea, vomiting, headache, dizziness, constipation, postural hypotension.
• Neuropsychiatric: hallucinations, confusion, depression, sleep attacks.
• Fibrotic reactions: pericardial, pleural, retroperitoneal fibrosis; cardiac valvulopathy.
• Cardiac: chest pain, vasospasm, arrhythmia.
• Other: peripheral oedema, fatigue, Raynaud’s phenomenon, epistaxis.

🧠 Clinical Pearls

• Cabergoline is highly effective in normalising prolactin and shrinking micro- and macroprolactinomas.
• In Parkinson’s disease, consider it as adjunctive therapy in fluctuating motor symptoms or as monotherapy in younger patients.
• Always screen for cardiac valvulopathy before initiating — fibrotic risk is cumulative and dose-related.
• Patients should be advised to report dyspnoea, chest pain, flank pain, or ankle swelling promptly — signs of fibrosis.
• Monitor behaviour — dopamine agonists can unmask or worsen impulse-control disorders.

📚 References

• BNF: Cabergoline
• NICE CKS: Prolactinoma
• UpToDate: “Dopamine agonists in Parkinson’s disease and hyperprolactinaemia.”
• MHRA Drug Safety Update: “Ergot-derived dopamine agonists and fibrotic reactions.”