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Pronunciation
(ca BER goe leen)
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in most animal studies when administered in maternally nontoxic doses. Treatment of hyperprolactinemia may restore fertility in a previously infertile woman. Because information concerning the use of cabergoline in pregnancy is limited, bromocriptine is generally recommended to treat hyperprolactinemia in women who wish to conceive. Based on preliminary data, cabergoline has not been shown to increase the risk of congenital malformations or miscarriages when used early in pregnancy (treatment was generally stopped once pregnancy was diagnosed). Not recommended for use in patients with pregnancy-induced hypertension unless benefit outweighs potential risk.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Interferes with lactation and should not be given to women postpartum who are breast-feeding or who are planning to breast-feed. Not indicated for the suppression of physiologic lactation.
Contraindications
Hypersensitivity to ergot derivatives; uncontrolled hypertension; history of pulmonary, pericardial, cardiac valvular or retroperitoneal fibrotic disorders
Warnings/Precautions
Concerns related to adverse effects:
• Cardiac valvular fibrosis: Cardiac valvular disease (mitral, aortic, tricuspid regurgitation) has been associated with cabergoline (a potent 5-HT2B agonist). Incidence may be higher for daily doses >2 mg and for duration of use ?6 months. Following diagnosis of fibrosis/valvulopathy, discontinuation of cabergoline may result in improvement in condition.
• Orthostatic hypotension: Initial doses >1 mg may cause orthostatic hypotension. Concurrent use with antihypertensives may increase risk.
• Pleural/retroperitoneal fibrosis: Rare cases of pleural effusion, pulmonary/retroperitoneal fibrosis have been reported with prolonged daily use.
• Psychiatric disorders: Pathological gambling, increased libido, and hypersexuality have been reported with use; generally reversible with dose reduction or discontinuation of treatment.
Disease-related concerns:
• Hepatic impairment: Use with caution and carefully monitor patients with hepatic impairment; extensively metabolized by the liver.
• Pregnancy-induced hypertension: Should not be used in patients with pregnancy-induced hypertension unless benefit outweighs potential risk.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions:
• Appropriate use: Not indicated for the inhibition or suppression of physiologic lactation; other dopamine agonists are associated with cases of hypertension, stroke, and seizures.
• Monitoring: In all patients, prolactin concentrations should be monitored monthly until normalized.
Adverse Reactions
>10%:
Central nervous system: Headache (26%), dizziness (15% to 17%)
Gastrointestinal: Nausea (27% to 29%)
1% to 10%:
Cardiovascular: Postural hypotension (4%), hypotension (1%), dependent edema (1%), edema (peripheral 1%), palpitation (1%), syncope (1%)
Central nervous system: Fatigue (5% to 7%), vertigo (1% to 4%), depression (3%), somnolence (2% to 5%), nervousness (1% to 2%), anxiety (1%), insomnia (1%), concentration impaired (1%), malaise (1%)
Dermatologic: Acne (1%), pruritus (1%)
Endocrine: Hot flashes (1% to 3%), breast pain (1% to 2%), dysmenorrhea (1%)
Gastrointestinal: Constipation (7% to 10%), abdominal pain (5%), dyspepsia (2% to 5%), vomiting (2% to 4%), xerostomia (2%), diarrhea (2%), flatulence (2%), anorexia (1%), throat irritation (1%), toothache (1%)
Neuromuscular & skeletal: Weakness (6% to 9%), pain (2%), paresthesia (1% to 2%), arthralgia (1%)
Ocular: Abnormal vision (1%), periorbital edema (1%)
Respiratory: Rhinitis (1%)
Miscellaneous: Flu-like syndrome (1%)
<1%: Confusion (in patients with Parkinson's disease [PD]), constrictive pericarditis (in PD patients), duodenal ulcer (in PD patients), dyskinesia (in PD patients), epistaxis, facial edema, gastric ulcer (in PD patients), hallucinations (in PD patients), heart failure (in PD patients), libido increased, pleural effusion (in PD patients), pulmonary fibrosis (in PD patients), weight gain/loss
Postmarketing and/or case reports: Aggression, alopecia, cardiac fibrosis, hypersexuality, pathological gambling, psychosis, valvulopathy
Drug Interactions
Efavirenz: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, the risk for peripheral vasospasm and ischemia may be increased. Risk X: Avoid combination
Itraconazole: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Posaconazole: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Serotonin 5-HT1D Receptor Agonists: Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Sibutramine: May enhance the serotonergic effect of Ergot Derivatives. This may cause serotonin syndrome. Risk X: Avoid combination
Voriconazole: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid products that enhance serotonin activity (includes SAMe [S-adenosylmethionine] and St John's wort); may increase the risk of serotonin syndrome.
Storage
Store at 20°C to 25°C (68°F to 77°F).
Mechanism of Action
Cabergoline is a long acting dopamine receptor agonist with a high affinity for D2 receptors; prolactin secretion by the anterior pituitary is predominantly under hypothalamic inhibitory control exerted through the release of dopamine. It is a potent 5-HT2B-receptor agonist, which may contribute to observed fibrotic/valvulopathic events.
Pharmacodynamics/Kinetics
Distribution: Extensive, particularly to the pituitary
Protein binding: 40% to 42%
Metabolism: Extensively hepatic via hydrolysis; minimal CYP mediated metabolism
Half-life elimination: 63-69 hours
Time to peak: 2-3 hours
Excretion: Primarily feces (~60%); urine (~22%, <4% as unchanged drug)
Dosage
Initial dose: Oral: 0.25 mg twice weekly; the dose may be increased by 0.25 mg twice weekly up to a maximum of 1 mg twice weekly according to the patient's serum prolactin level. Dosage increases should not occur more rapidly than every 4 weeks. Once a normal serum prolactin level is maintained for 6 months, the dose may be discontinued and prolactin levels monitored to determine if cabergoline is still required. The durability of efficacy beyond 24 months of therapy has not been established.
Elderly: No dosage recommendations suggested, but start at the low end of the dosage range
Dosage adjustment in renal dysfunction: No adjustment required.
Dosage adjustment in hepatic dysfunction:
Mild-to-moderate dysfunction (Child-Pugh Class B): No adjustment required
Severe dysfunction (Child-Pugh Class C): Use caution; significant increase in AUC
Monitoring Parameters
Blood pressure (both sitting/supine and standing); serum prolactin level, echocardiogram with long-term use (>6 months)
Additional Information
Bromocriptine and cabergoline are the only drugs indicated for the treatment of hyperprolactinemia. In the largest comparative clinical trial, prolactin levels normalized in 77% of patients treated with cabergoline compared to 59% of patients treated with bromocriptine. In that trial, 3% of patients discontinued treatment due to adverse effects in the cabergoline group versus 12% of patients in the bromocriptine group. In addition to the improved safety and efficacy profile, cabergoline (administered twice weekly) is more convenient than bromocriptine (administered 1-3 times/day) for patients to take.
Cardiovascular Considerations
Valvular damage may be mediated through the serotonin receptor subtype 5-HT2B as proliferation of fibroblasts occurs within valve tissue when stimulated. Some experts recommend avoiding prescribing medications that are potent 5-HT2B-receptor agonists.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation), throat irritation, and toothache.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common; may cause depression
Mental Health: Effects on Psychiatric Treatment
Antipsychotics may decrease the therapeutic effects of cabergoline; avoid combination
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 0.5 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Cabergoline)
0.5 mg (8): $265.97
References
Bronstein MD, “Prolactinomas and pregnancy,” Pituitary, 2005, 8(1):31-8.
European Multicentre Study Group for Cabergoline in Lactation Inhibition, “Single Dose Cabergoline Versus Bromocriptine in Inhibition of Puerperal Lactation: Randomised, Double-Blind, Multicentre Study,” Br Med J, 1991, 302:1367-71.
Ferrari C, Paracchi A, Mattei AM, et al, “Cabergoline in the Long-Term Therapy of Hyperprolactinemic Disorders,” Acta Endocrinol (Copenh), 1992, 126:489-94.
Giusti M, Porcella E, Carraro A, et al, “A Cross-Over Study With the Two Novel Dopaminergic Drugs Cabergoline and Quinagolide in Hyperprolactinemic Patients,” J Endocrinol Invest, 1994, 17:51-7.
Rains CP, Bryson HM, and Fitton A, “Cabergoline: A Review of Its Pharmacological Properties and Therapeutic Potential in the Treatment of Hyperprolactinemia and Inhibition of Lactation,” Drugs, 1995, 49:255-79.
Ricci E, Parazzini F, Motta T, et al, “Pregnancy Outcome After Cabergoline Treatment in Early Weeks of Gestation,” Reprod Toxicol, 2002, 16(6):791-3.
Robert E, Musatti L, Piscitelli G, et al, “Pregnancy Outcome After Treatment With the Ergot Derivative, Cabergoline,” Reprod Toxicol, 1996,10(4):333-7.
Roth BL, “Drugs and Valvular Heart Disease,” N Engl J Med, 2007, 356(1):6-9.
Schade R, Andersohn F, Suissa S, et al, “Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation,” N Engl J Med, 2007, 356(1):29-38.
Webster J, Piscitelli G, Polli A, et al, “A Comparison of Cabergoline and Bromocriptine in the Treatment of Hyperprolactinemic Amenorrhea,” N Engl J Med, 1994, 331:904-9.
Webster J, Piscitelli G, Polli A, et al, “Dose-Dependent Suppression of Serum Prolactin by Cabergoline in Hyperprolactinaemia: A Placebo Controlled, Double Blind, Multicentre Study,” Clin Endocrinol (Oxf), 1992, 68:1201-6.
Webster J, Piscitelli G, Polli A, et al, “The Efficacy and Tolerability of Long-Term Cabergoline Therapy in Hyperprolactinaemic Disorders: An Open, Uncontrolled, Multicentre Study,” Clin Endocrinol (Oxf), 1993, 39:323-9.
Zanettini R, Antonini A, Gatto G, et al, “Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson's Disease,” N Engl J Med2007, 356(1):39-46.
International Brand Names
Lexi-Comp.com
Last full review/revision June 2009
Content last modified June 2009
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