Cabergoline

Clinical data
Trade names	Dostinex, others
AHFS/Drugs.com	Monograph
License data	US FDA: CABERGOLINE
Routes of administration	Oral
ATC code	G02CB03 (WHO) N04BC06 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	First-pass effect seen; absolute bioavailability unknown
Protein binding	Moderately bound (40–42%); concentration-independent
Metabolism	Hepatic, predominately via hydrolysis of the acylurea bond or the urea moiety
Elimination half-life	63–69 hours (estimated)
Excretion	Urine (22%), feces (60%)
Identifiers
show IUPAC name
CAS Number	81409-90-7
PubChem CID	54746
IUPHAR/BPS	37
DrugBank	DB00248
ChemSpider	49452
UNII	LL60K9J05T
KEGG	D00987
ChEBI	CHEBI:3286
ChEMBL	ChEMBL1201087
CompTox Dashboard (EPA)	DTXSID6022719
ECHA InfoCard	100.155.380
Chemical and physical data
Formula	C26H37N5O2
Molar mass	451.615 g·mol−1
3D model (JSmol)	Interactive image
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Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth.

Cabergoline is an ergot derivative and a potent dopamine D₂ receptor agonist.

Cabergoline was patented in 1980 and approved for medical use in 1993.

Medical uses[edit]

• Lactation suppression
• Hyperprolactinemia
• Adjunctive therapy of prolactin-producing pituitary gland tumors (prolactinomas);
• Monotherapy of Parkinson's disease in the early phase;
• Combination therapy, together with levodopa and a decarboxylase inhibitor such as carbidopa, in progressive-phase Parkinson's disease;
• In some countries also: ablactation and dysfunctions associated with hyperprolactinemia (amenorrhea, oligomenorrhea, anovulation, nonpuerperal mastitis and galactorrhea);
• Treatment of uterine fibroids.
• Adjunctive therapy of acromegaly, cabergoline has low efficacy in suppressing growth hormone levels and is highly efficient in suppressing hyperprolactinemia that is present in 20-30% of acromegaly cases; growth hormone and prolactin are similar structurally and have similar effects in many target tissues, therefore targeting prolactin may help symptoms when growth hormone secretion can not be sufficiently controlled by other methods;

Cabergoline is frequently used as a first-line agent in the management of prolactinomas due to its higher affinity for D₂ receptor sites, less severe side effects, and more convenient dosing schedule than the older bromocriptine, though in pregnancy bromocriptine is often still chosen since there is less data on safety in pregnancy for cabergoline.

Off-label[edit]

It has at times been used as an adjunct to SSRI antidepressants as there is some evidence that it counteracts certain side effects of those drugs, such as reduced libido and anorgasmia. It also has been suggested that it has a possible recreational use in reducing or eliminating the male refractory period, thereby allowing men to experience multiple ejaculatory orgasms in rapid succession, and at least two scientific studies support those speculations. Additionally, a systematic review and meta-analysis concluded that prophylactic treatment with cabergoline reduces the incidence, but not the severity, of ovarian hyperstimulation syndrome (OHSS), without compromising pregnancy outcomes, in females undergoing stimulated cycles of in vitro fertilization (IVF). Also, a study on rats found that cabergoline reduces voluntary alcohol consumption, possibly by increasing GDNF expression in the ventral tegmental area.It may be used in the treatment of restless legs syndrome.^{[citation needed]}

Pregnancy and lactation

Side effects are mostly dose dependent. Much more severe side effects are reported for treatment of Parkinson's disease and (off-label treatment) for restless leg syndrome which both typically require very high doses. The side effects are considered mild when used for treatment of hyperprolactinemia and other endocrine disorders or gynecologic indications where the typical dose is one hundredth to one tenth that for Parkinson's disease.^{[citation needed]}

Cabergoline requires slow dose titration (2–4 weeks for hyperprolactinemia, often much longer for other conditions) to minimise side effects. The extremely long bioavailability of the medication may complicate dosing regimens during titration and require particular precautions.

Cabergoline is considered the best tolerable option for hyperprolactinemia treatment although the newer and less tested quinagolide may offer similarly favourable side effect profile with quicker titration times.

Approximately 200 patients with newly diagnosed Parkinson's disease participated in a clinical study of cabergoline monotherapy. Seventy-six (76) percent reported at least one side effect. These side effects were chiefly mild or moderate:

• GI tract: Side effects were extremely frequent. Fifty-three percent of patients reported side effects. Very frequent: Nausea (30%), constipation (22%), and dry mouth (10%). Frequent: Gastric irritation (7%), vomiting (5%), and dyspepsia (2%).
• Psychiatric disturbances and central nervous system (CNS): Altogether 51 percent of patients were affected. Very frequent: Sleep disturbances (somnolence 18%, insomnia 11%), vertigo (27%), and depression (13%). Frequent: dyskinesia (4%) and hallucinations (4%).
• Cardiovascular: Approximately 30 percent of patients experienced side effects. Most frequent were hypotension (10%), peripheral edema (14%) and non-specific edema (2%). Arrhythmias were encountered in 4.8%, palpitations in 4.3%, and angina pectoris in 1.4%.

In a combination study with 2,000 patients also treated with levodopa, the incidence and severity of side effects was comparable to monotherapy. Encountered side effects required a termination of cabergoline treatment in 15% of patients. Additional side effects were infrequent cases of hematological side effects, and an occasional increase in liver enzymes or serum creatinine without signs or symptoms.

As with other ergot derivatives, pleuritis, exudative pleura disease, pleura fibrosis, lung fibrosis, and pericarditis are seen. These side effects are noted in less than 2% of patients. They require immediate termination of treatment. Clinical improvement and normalization of X-ray findings are normally seen soon after cabergoline withdrawal. It appears that the dose typically used for treatment of hyperprolactinemia is too low to cause this type of side effects.

Valvular heart disease

In two studies published in the New England Journal of Medicine on January 4, 2007, cabergoline was implicated along with pergolide in causing valvular heart disease. As a result of this, the FDA removed pergolide from the U.S. market on March 29, 2007.^[14] Since cabergoline is not approved in the U.S. for Parkinson's Disease, but for hyperprolactinemia, the drug remains on the market. The lower doses required for treatment of hyperprolactinemia have been found to be not associated with clinically significant valvular heart disease or cardiac valve regurgitation.^[