Trade names Cabaser, Dostinex License data US FDA: CABERGOLINE CAS ID 81409-90-7 | AHFS/Drugs.com Monograph Routes ofadministration Oral Molar mass 451.604 g/mol | |
Pregnancycategory US: B (No risk in non-human studies) ATC code G02CB03 (WHO) N04BC06 (WHO) |
Cabergoline (brand names Dostinex and others), an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. Rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph (prolactin) cells. It 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.
Contents
- Cabergoline for bodybuilding and sex drive
- Medical uses
- Off label
- Pregnancy and lactation
- Contraindications and precautions
- Side effects
- Valvular heart disease
- Interactions
- Pharmacology
- Pharmacokinetics
- Mechanism of action
- Research
- History
- References
Cabergoline for bodybuilding and sex drive
Medical uses
Off-label
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 online 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 one scientific study supports 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.
Pregnancy and lactation
Relatively little is known about the effects of this medication during pregnancy and lactation. In some cases the related bromocriptine may be an alternative when pregnancy is expected.
Contraindications and precautions
Side effects
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 10–100 times smaller than for Parkinson's disease.
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-nine (79) percent reported at least one side effect. These side effects were chiefly mild or moderate:
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. 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.
Interactions
No interactions were noted with levodopa or selegiline. The drug should not be combined with other ergot derivatives. Dopamine antagonists such as antipsychotics and metoclopramide counteract some effects of cabergoline. The use of antihypertensive drugs should be intensively monitored because excessive hypotension may result from the combination.
Pharmacology
Although cabergoline is commonly described principally as a dopamine D2 receptor agonist, it also possesses significant affinity for the D3, D4, 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C, α2B- receptors, and moderate/low affinity for the D1 and 5-HT7 receptors. Cabergoline functions as an agonist at all of these receptors except for 5-HT7 and α2B-, where it acts as an antagonist.
Pharmacokinetics
Following a single oral dose, resorption of cabergoline from the gastrointestinal (GI) tract is highly variable, typically occurring within 0.5 to 4 hours. Ingestion with food does not alter its absorption rate. Human bioavailability has not been determined since the drug is intended for oral use only. In mice and rats the absolute bioavailability has been determined to be 30 and 63 percent, respectively. Cabergoline is rapidly and extensively metabolized in the liver and excreted in bile and to a lesser extent in urine. All metabolites are less active than the parental drug or inactive altogether. The human elimination half-life is estimated to be 63 to 68 hours in patients with Parkinson's disease and 79 to 115 hours in patients with pituitary tumors. Average elimination half-life is 80 hours.
The therapeutic effect in treatment of hyperprolactinemia will typically persist for at least 4 weeks after cessation of treatment.
Mechanism of action
Cabergoline is a long-acting dopamine D2 receptor agonist and in vitro rat studies show a direct inhibitory effect on the prolactin secretion in the pituitary's lactotroph cells. Cabergoline decreased serum prolactin levels in reserpinized rats.
Receptor binding studies indicate a low affinity for dopamine D1 receptors, α1-adrenergic receptors, and α2-adrenergic receptors.
Research
Cabergoline was studied in one person with Cushing's disease, to lower ACTH levels and cause regression of ACTH producing pituitary adenomas.
History
Cabergoline was first synthesized by scientists working for the Italian drug company Farmitalia-Carlo Erba in Milan who were experimenting with semisynthetic derivatives of the ergot alkaloids, and a patent application was filed in 1980. The first publication was a scientific abstract at the Society for Neuroscience meeting in 1991.
Farmitalia-Carlo Erba was acquired by Pharmacia in 1993, which in turn was acquired by Pfizer in 2003.
Cabergoline was first marketed in The Netherlands as Dostinex in 1992. The drug was approved by the FDA on December 23, 1996. It went generic in late 2005 following US patent expiration.