Cabergoline

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Introduction and Phrmacology

Cabergoline (brand names Dostinex® and Cabaser®), an ergot-derivative, is a potent dopamine receptor agonist on D2-Receptors. It also acts on dopamine-receptors in lactophilic hypothalamus cells and causes thereby a suppression of the prolactin-production in pituitary gland.

Pharmacokinetics

Following an oral single dose the drug is resorbed within 0.5 to 4 hours from the GI-Tract with considerable interindividual differences. Meals do not alter the absorption characteristic. Human bioavailibility was not determined, because the drug is intended for oral use only. In mice and rats the absolute bioavailability was 30 and 63%, respectively. Cabergoline is rapidly and to a great extend metabolized in the liver and excreted in bile and far less in urine. All metabolites are less active than the parental drug or inactive. The human elimination halflife is estimated to be 63 to 68 hours in patients with M. Parkinson and 79 to 115 hours in patients with pituitary tumors.

Carcinogenity

In rodents a dose dependent increase in malignant tumors has been found. They are thought to be species-specific. No clinical data exists on carcinogenity in humans.

Uses

• Monotherapy of Morbus Parkinson in the early phase.
• Combination therapy of Morbus Parkinson in the progressive phase together with levodopa and a decarboxylase-inhibitor like carbidopa.
• Adjunctive therapy of prolactin-producing tumors of the pituitary gland (microprolactinomes).
• In some countries also : ablactation and dysfunctions associated with hyperprolactinemia (amenorrhea, oligomenorrhea, anovulation, und galactorrhea).

Off-Label/Recreational Uses

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.

Contraindications and Precautions

• Hypersensitivity to ergot-derivatives
• Pediatric Patients (no clinical experience)
• Severely impaired liver function or cholestasis
• Comedication with drugs metabolized mainly by CYP P450 such as erythromycin and ketoconazole, because increased plasma levels of cabergoline may result.
• Cautions : severe cardiovascular disease, Raynaud's Syndrome, gastroduodenal ulcers, active gastrointestinal bleeding, hypotension.

Pregnancy and Lactation

• Pregnancy : Approximately 100 female patients became pregnant under therapy with cabergoline for hyperprolactinemic conditions. The incidence of spontanous aborts and congenital abnormalities was comparable to nontreated patients. Nonetheless womem, wishing to become pregnant, should wait a safety period of 4 weeks after discontinuation of cabergoline. Patients becoming pregant under therapy should terminate cabergoline immediately, if possible.
• Lactation : In rats cabergoline was found in the maternal milk. Since it is not known, if this effect is also seen in humans, lactating women should not be treated.

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