Cabolin

Approved Indications:

• Hyperprolactinemia:
• Treatment of hyperprolactinemic disorders, either idiopathic or due to prolactin-secreting pituitary adenomas (prolactinomas), including:
• Amenorrhea
• Galactorrhea
• Infertility
• Both in women and men
• Inhibition of Physiological Lactation:
• For the prevention or suppression of lactation due to medical reasons (e.g., stillbirth, miscarriage, or when breastfeeding is contraindicated)
• Parkinson’s Disease (Off-label/Clinically Accepted Use):
• Used in early-stage or adjunctive therapy in Parkinson’s disease, especially as an ergot-derived dopamine agonist, although its use has declined due to cardiac risks.
• Often considered in patients who cannot tolerate levodopa or require adjunctive treatment for wearing-off effects.

For Hyperprolactinemia (Adults):

• Initial Dose: 0.25 mg twice weekly.
• Titration: Increase by 0.25 mg twice weekly every 4 weeks based on serum prolactin levels and clinical response.
• Maximum Dose: Up to 1 mg twice weekly (2 mg/week); doses up to 4.5 mg/week may be used in resistant cases.

For Inhibition of Lactation:

• Single Dose: 1 mg orally as a single dose within the first 24 hours postpartum.

For Parkinson’s Disease (Off-label Use):

• Initial Dose: 0.5 mg/day (can be divided into two doses).
• Maintenance Dose: Usually 2–6 mg/day.
• Maximum Dose: Up to 6 mg/day.
• Titrate gradually every 7–14 days to minimize side effects.

Special Populations:

• Hepatic Impairment: Use with caution; no formal dose adjustment guidelines, but hepatic metabolism may affect clearance.
• Renal Impairment: No dose adjustment required, but monitor closely.
• Elderly: Use the lowest effective dose; increased sensitivity to dopaminergic effects.

Route of Administration:

• Oral administration only.
• Take with food to reduce GI side effects.

Cabergoline is a long-acting dopamine D2 receptor agonist. It inhibits prolactin secretion by directly stimulating dopamine receptors in the anterior pituitary lactotroph cells, where dopamine acts as the primary prolactin-inhibiting factor. In Parkinson’s disease, it exerts antiparkinsonian effects by mimicking dopamine activity in the nigrostriatal pathway. Its long half-life ensures sustained receptor stimulation, reducing prolactin levels and managing motor symptoms effectively.

• Absorption: Rapid oral absorption; peak plasma concentration in 2–3 hours.
• Bioavailability: Not precisely determined due to high first-pass metabolism but therapeutically effective at low doses.
• Distribution: High volume of distribution; >40% protein bound.
• Metabolism: Extensively metabolized in the liver, primarily via hydrolysis of the acylurea bond and other non-CYP450 pathways.
• Active Metabolites: None with significant pharmacological activity.
• Elimination Half-Life:
• Hyperprolactinemia: ~63–69 hours
• Parkinson’s disease (higher doses): ~79–115 hours
• Excretion: Mainly fecal (~60%), with ~20% excreted in urine, mostly as metabolites.

• Pregnancy:
• Former FDA Category B: Animal studies do not show fetal risk, and limited human data suggest low teratogenic risk.
• May be used in pregnancy if benefits outweigh risks, especially for prolactinomas.
• Discontinue once pregnancy is confirmed unless tumor control is necessary.
• Lactation:
• Contraindicated in breastfeeding as it suppresses prolactin and milk production.
• Unknown if excreted in human milk; potential risk to infants due to dopamine agonism.

• Primary Class: Dopamine Agonist
• Subclass: Ergot Derivative
• Other Categories: Prolactin Inhibitor, Antiparkinsonian Agent (off-label)

• Hypersensitivity to Cabergoline, ergot alkaloids, or any excipient
• History of pulmonary, pericardial, or retroperitoneal fibrotic disorders
• Uncontrolled hypertension
• Pregnancy (when used for lactation suppression)
• Severe hepatic impairment
• History of cardiac valvulopathy (confirmed by echocardiogram)

• Cardiac Valvulopathy: Associated with valvular fibrosis; perform baseline and periodic echocardiograms.
• Fibrotic Reactions: Risk of pulmonary, peritoneal, and retroperitoneal fibrosis with prolonged use.
• Hypotension: Orthostatic hypotension may occur, particularly during dose titration.
• Psychiatric Effects: May cause impulse control disorders (gambling, hypersexuality) and hallucinations.
• Hepatic Monitoring: Use cautiously in liver dysfunction; monitor liver function periodically.
• Withdrawal Effects: Dopaminergic withdrawal may cause neuroleptic malignant-like syndrome.
• Pregnancy Considerations: Discontinue when pregnancy is detected unless continued use is justified.

Common (≥5%):

• Gastrointestinal: Nausea, constipation, abdominal pain
• Neurologic: Dizziness, headache, somnolence
• Cardiovascular: Hypotension, palpitations
• Psychiatric: Depression, anxiety

Less Common (1–5%):

• Vomiting
• Peripheral edema
• Hot flushes
• Visual disturbances

Serious/Rare:

• Cardiac valve disorders (aortic, mitral, tricuspid regurgitation)
• Pulmonary fibrosis
• Pericarditis or pericardial effusion
• Psychosis or hallucinations
• Impulse control disorders (e.g., compulsive shopping, eating)

Timing & Dose Dependence:

• Valvulopathy and fibrosis are dose-dependent and more common with long-term, high-dose use (e.g., Parkinson’s doses).

• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin):
• May increase Cabergoline plasma levels and toxicity risk.
• Dopamine Antagonists (e.g., metoclopramide, antipsychotics):
• Reduce Cabergoline efficacy by counteracting dopamine agonism.
• Ergot Alkaloids or Vasoconstrictors: Risk of additive vasospasm or toxicity.
• Alcohol: May potentiate orthostatic hypotension or CNS effects.
• Antihypertensives: Additive hypotensive effects; monitor closely.

• Valvulopathy Warnings Enhanced:
• Updated guidelines emphasize baseline and periodic echocardiographic monitoring for patients on long-term or high-dose therapy (especially Parkinson’s patients).
• European Medicines Agency (EMA):
• Recommends stricter cardiac evaluation before and during treatment, especially when doses >1 mg/week are used.
• Prolactinoma Management Guidelines:
• Still considered first-line therapy for prolactin-secreting adenomas due to high efficacy and tolerability at low doses.

• Temperature: Store at 20°C to 25°C (68°F to 77°F).
• Excursions: Permitted between 15°C and 30°C.
• Protection: Protect from moisture and light.
• Packaging: Keep in tightly closed containers.
• Handling: No shaking or refrigeration needed.