DOSTINEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DOSTINEX (DOSTINEX).
Cabergoline is a long-acting dopamine D2 receptor agonist that inhibits prolactin secretion by binding to D2 receptors on lactotroph cells in the anterior pituitary.
| Metabolism | Extensively metabolized in the liver, primarily via hydrolysis of the acylurea bond; CYP3A4 is involved in minor hydroxylation pathways. |
| Excretion | Cabergoline is extensively metabolized in the liver, primarily via CYP3A4. Elimination is predominantly fecal (60%) and renal (20%) as metabolites, with <4% as unchanged drug. Biliary excretion contributes to fecal elimination. |
| Half-life | The terminal elimination half-life is 63–69 hours in healthy volunteers and 79–115 hours in patients with hyperprolactinemia, allowing once- or twice-weekly dosing. The long half-life reflects slow dissociation from D2 receptors and enterohepatic recirculation. |
| Protein binding | Approximately 41–42% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The apparent volume of distribution is approximately 150–200 L, indicating extensive tissue distribution. In L/kg (assuming 70 kg), Vd ≈ 2.1–2.9 L/kg. This large Vd suggests sequestration in tissues, including the pituitary. |
| Bioavailability | Oral bioavailability is approximately 50–60% due to first-pass metabolism. Food does not significantly affect absorption. |
| Onset of Action | Oral: Suppression of prolactin occurs within 3 hours, with maximal effect at 48–72 hours. Clinical effect on galactorrhea may be noticed within 1–2 weeks. |
| Duration of Action | A single oral dose suppresses prolactin levels for up to 14 days in most patients. Duration correlates with half-life; therapeutic effect on prolactinoma shrinkage and fertility restoration is sustained over weeks to months of therapy. |
0.25 mg orally twice weekly, with a minimum of 2 days between doses; may increase by 0.25 mg twice weekly every 4 weeks up to a maximum of 1 mg twice weekly.
| Dosage form | TABLET |
| Renal impairment | No specific recommendations; use caution in severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | No specific recommendations; use caution in severe hepatic impairment (Child-Pugh class C) due to reduced clearance. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established; not recommended. |
| Geriatric use | No specific dose adjustment; monitor for orthostatic hypotension and neuropsychiatric effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DOSTINEX (DOSTINEX).
| Breastfeeding | Excreted into human milk. Peak milk concentration ~0.15-0.25 ng/mL after 0.25 mg oral dose. M/P ratio unknown. Due to potential for suppression of lactation and unknown infant effects, contraindicated in breastfeeding women. Discontinue nursing or avoid drug. |
| Teratogenic Risk | Category B: Animal studies (rats, rabbits) at doses up to 2.5 mg/kg/day showed no teratogenic effects but embryotoxicity at high doses. No adequate human studies. Post-marketing reports of spontaneous abortion and congenital anomalies (limb defects, cardiac) but causal relationship unestablished. Avoid in pregnancy unless benefit outweighs risk. Use only after excluding pregnancy and using effective contraception during treatment until 1 month after discontinuation. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Uncontrolled hypertension","Preeclampsia or eclampsia","Known hypersensitivity to ergot derivatives","History of pulmonary, pericardial, or retroperitoneal fibrotic disorders"]
| Precautions | ["Risk of valvulopathy and cardiac fibrosis with long-term use, especially at high cumulative doses","May cause hypotension, syncope, or orthostatic hypotension","Monitor for pleural effusion, pulmonary fibrosis, and pericarditis","Impulse control disorders (e.g., pathological gambling, hypersexuality)","Somnolence and sudden sleep onset; caution when driving"] |
| Food/Dietary | No specific food restrictions. However, high-fat meals may increase absorption, but no dose adjustment is required. Avoid alcohol due to increased risk of dizziness and gastrointestinal upset. Grapefruit juice may inhibit CYP3A4 and increase cabergoline levels; consider avoiding large quantities. |
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| Fetal Monitoring | Monitor pregnancy test before initiation and monthly during treatment. Monitor for signs of pregnancy. During pregnancy, perform fetal ultrasound for cardiac and limb anomalies if exposed. Monitor maternal blood pressure (risk of hypertension, preeclampsia), and for symptoms of ergotism (nausea, headache, Raynaud's phenomenon). |
| Fertility Effects | In women with hyperprolactinemia, restores ovulation and fertility by normalizing prolactin levels. May induce pregnancy. No evidence of long-term adverse effects on fertility in men or women. Discontinue use once pregnancy is confirmed. |
| Clinical Pearls | Dostinex (cabergoline) is a long-acting dopamine D2 receptor agonist used primarily for hyperprolactinemia. Its half-life of 63-69 hours allows once or twice weekly dosing. Monitor for valvular heart disease with echocardiography before and during therapy due to risk of fibrotic reactions, especially at high doses used in Parkinson's disease. Avoid concurrent use with CYP3A4 inhibitors (e.g., macrolides, azole antifungals) that can increase cabergoline levels. Titrate dose gradually to minimize orthostatic hypotension and gastrointestinal side effects. |
| Patient Advice | Take exactly as prescribed, typically once or twice per week; do not double doses if missed. Take with food if nausea occurs. Avoid alcohol as it may increase side effects. Report any shortness of breath, cough, chest pain, or swelling of extremities immediately (signs of valvulopathy). Do not drive or operate machinery until you know how the medication affects you, as it may cause dizziness or drowsiness. Women who may become pregnant should use effective contraception; stop cabergoline if pregnancy is confirmed. Inform all healthcare providers about this medication, including before any surgery or dental procedures. Keep out of reach of children and store at room temperature. |