CABERGOLINE
Clinical safety rating: safe
Animal studies have demonstrated safety
Cabergoline is a long-acting dopamine D2 receptor agonist that inhibits prolactin secretion by the anterior pituitary gland.
| Metabolism | Extensively metabolized in the liver, primarily by hydrolysis and minor CYP3A4 involvement. |
| Excretion | Approximately 60-70% of the dose is excreted in feces (primarily as unchanged drug and metabolites), with about 20-30% excreted renally (mostly as metabolites). |
| Half-life | Terminal elimination half-life is 63-68 hours in healthy subjects, allowing for once- or twice-weekly dosing. In hepatic impairment, half-life may be prolonged. |
| Protein binding | 40-42% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 100-150 L/kg, indicating extensive tissue distribution; Vd is large (≥100 L/kg) due to high lipophilicity and tissue binding. |
| Bioavailability | Oral bioavailability is about 40-45% (range 30-60%) due to first-pass metabolism. No parenteral formulations are commonly used. |
| Onset of Action | Oral: Onset of prolactin-lowering effect occurs within 3 hours, with maximal suppression at 12-24 hours post-dose. |
| Duration of Action | Duration of prolactin suppression is up to 14 days after a single dose, enabling weekly or twice-weekly dosing. Clinical effects on hyperprolactinemia persist with regular dosing. |
0.25 mg orally twice weekly, up to 1 mg twice weekly; for hyperprolactinemia, initial 0.25 mg twice weekly, titrate by 0.25 mg every 4 weeks based on prolactin levels.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment recommended for mild to moderate renal impairment (CrCl >10 mL/min); avoid use in severe renal impairment (CrCl <10 mL/min) due to lack of data. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh class C) as elimination may be reduced. |
| Pediatric use | Not FDA approved for pediatric use; limited data: 0.025-0.05 mg/kg once weekly, titrated cautiously based on prolactin levels; maximum 0.1 mg/kg weekly. |
| Geriatric use | No specific adjustment recommended; start at lower end of dosing range (0.25 mg twice weekly) due to potential for increased sensitivity and age-related decline in renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other drugs that lower blood pressure may have additive effects Ergot-related drugs may cause fibrosis of cardiac valves with long-term use.
| Breastfeeding | Cabergoline suppresses lactation; contraindicated in breastfeeding women because it reduces milk production. If used, discontinue breastfeeding or avoid drug. M/P ratio not established; drug is excreted in rat milk, unknown in humans. |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; limited human data. In first trimester, theoretical risk of ergot alkaloid-induced uteroplacental vasoconstriction may cause fetal hypoxia; use only if benefit outweighs risk. Second and third trimesters: risk of postpartum hemorrhage and uterine atony if used for lactation suppression; avoid in pregnancy due to potential for fetal harm from dopamine agonist effects. |
■ FDA Black Box Warning
Cabergoline is associated with an increased risk of cardiac valve regurgitation, especially at high doses used for Parkinson's disease. The risk appears lower at doses used for hyperprolactinemia, but caution is advised.
| Common Effects | Nausea |
| Serious Effects |
["Hypersensitivity to cabergoline or ergot derivatives","Uncontrolled hypertension","History of cardiac valvular disease","Pregnancy: use only if clearly needed (category B)"]
| Precautions | ["Cardiac valvulopathy: monitor with echocardiography before and during therapy","Pleural, pericardial, and retroperitoneal fibrosis","Postural hypotension","Impulse control disorders (e.g., pathological gambling, hypersexuality)","Remission of prolactinomas may reduce pituitary function"] |
| Food/Dietary |
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| Fetal Monitoring | Monitor maternal blood pressure, pulse, and signs of uterine contractions throughout therapy. Fetal monitoring (ultrasound) for growth and placental insufficiency if exposed during second/third trimester. Assess for signs of postpartum hemorrhage if used near term. |
| Fertility Effects | Cabergoline restores ovulatory function in hyperprolactinemic women by reducing prolactin levels, thereby improving fertility. No direct adverse effects on fertility; may cause spontaneous abortion or ectopic pregnancy risk due to improved fertility. |
| Avoid high-fat meals that may increase absorption variability. No specific food restrictions, but take consistently with meals to maintain stable levels. Grapefruit juice may theoretically increase cabergoline exposure (CYP3A4 inhibition); avoid excessive consumption. |
| Clinical Pearls | Start with 0.25 mg twice weekly, titrate by 0.25 mg every 2-4 weeks based on prolactin levels and tolerability. Maximum dose typically 1 mg twice weekly. May cause orthostatic hypotension; caution when rising from supine position. Use lowest effective dose to minimize risk of valvulopathy, especially with cumulative doses >2 mg/day. Discontinue if signs of cardiac fibrosis. Monitor for impulse control disorders (e.g., hypersexuality, gambling). Avoid in patients with uncontrolled hypertension or pre-existing cardiac valvular disease. |
| Patient Advice | Take with food to reduce gastrointestinal upset. · Avoid alcohol as it may increase side effects like dizziness or nausea. · Rise slowly from sitting or lying positions to prevent fainting. · Report any new shortness of breath, swelling, or chest pain immediately. · Notify your doctor if you experience unusual urges (gambling, sex, spending). · Do not drive or operate machinery if you feel dizzy or drowsy. · Take exactly as prescribed; do not double the dose if missed. · Store at room temperature away from moisture and heat. |