Reproduction studies have been performed with cabergoline in mice, rats, and rabbits administered by gavage. (Multiples of the maximum recommended human dose in this section are calculated on a body surface area basis using total mg/m /week for animals and mg/m /week for a 50 kg human.)
There were maternotoxic effects but no teratogenic effects in mice given cabergoline at doses up to 8 mg/kg/day (approximately 55 times the maximum recommended human dose) during the period of organogenesis.
A dose of 0.012 mg/kg/day (approximately 1/7 the maximum recommended human dose) during the period of organogenesis in rats caused an increase in post-implantation embryofetal losses. These losses could be due to the prolactin inhibitory properties of cabergoline in rats. At daily doses of 0.5 mg/kg/day (approximately 19 times the maximum recommended human dose) during the period of organogenesis in the rabbit, cabergoline caused maternotoxicity characterized by a loss of body weight and decreased food consumption. Doses of 4 mg/kg/day (approximately 150 times the maximum recommended human dose) during the period of organogenesis in the rabbit caused an increased occurrence of various malformations. However, in another study in rabbits, no treatment-related malformations or embryofetotoxicity were observed at doses up to 8 mg/kg/day (approximately 300 times the maximum recommended human dose).
In rats, doses higher than 0.003 mg/kg/day (approximately 1/28 the maximum recommended human dose) from 6 days before parturition and throughout the lactation period inhibited growth and caused death of offspring due to decreased milk secretion.
There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from cabergoline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Use for the inhibition or suppression of physiologic lactation is not recommended.
The prolactin-lowering action of cabergoline suggests that it will interfere with lactation. Due to this interference with lactation, should not be given to women postpartum who are breastfeeding or who are planning to breastfeed.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
- Lactation suppression
- 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.
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.
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. Pregnancy: available preliminary data indicates a somewhat increased rate of congenital abnormalities in patients who became pregnant while treated with cabergoline. However, one study concluded that “foetal exposure to cabergoline through early pregnancy does not induce any increase in the risk of miscarriage or foetal malformation.”
- Lactation: In rats cabergoline was found in the maternal milk. Since it is not known if this effect also occurs in humans, breastfeeding is usually not recommended if/when treatment with cabergoline is necessary.
- Lactation suppression: In some countries cabergoline is sometimes used as a lactation suppressant. It is also used in veterinary medicine to treat false pregnancy in dogs.