Cabergoline 0.25 mg · Tablets

Cabergoline is an ergot derivative and dopamine receptor agonist with a high affinity for D2 receptors. Results of in vitro studies demonstrate that cabergoline exerts a direct inhibitory effect on the secretion of prolactin by rat pituitary lactotrophs. Cabergoline decreased serum prolactin levels in reserpinized rats. Receptor-binding studies indicate that cabergoline has low affinity for dopamine D1, α1- and α2-adrenergic, and 5-HT1- and 5-HT2-serotonin receptors.

Absorption — The time to reach maximum cabergoline plasma concentration was 2 to 3 hours after single oral doses of 0.5 mg to 1.5 mg (1.5 times the maximum recommended dose) of CABERGOLINE in healthy subjects. Following dosing of CABERGOLINE between 0.5 mg to 7 mg (7 times the maximum recommended dose), cabergoline plasma levels appeared to be dose-proportional. The absolute bioavailability of cabergoline is unknown. A significant fraction of the administered dose undergoes a first-pass effect.

Effect of Food: High-fat food did not alter the pharmacokinetics of cabergoline [see Dosage and Administration (2.2)].

Distribution — Protein binding of cabergoline was 40% to 42%.

Elimination — The elimination half-life of cabergoline estimated from urinary data of 12 healthy subjects ranged between 63 to 69 hours.

Metabolism: Cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond or the urea moiety. Hydrolysis of the acylurea or urea moiety abolishes the prolactin-lowering effect of cabergoline, and major metabolites identified thus far do not contribute to the therapeutic effect.

Excretion: After oral dosing of radioactive cabergoline to 5 healthy volunteers, approximately 22% and 60% of the dose was excreted within 20 days in the urine and feces, respectively. Less than 4% of the dose was excreted unchanged in the urine. Nonrenal and renal clearances for cabergoline are about 3.2 L/min and 0.08 L/min, respectively. Urinary excretion in hyperprolactinemic patients was similar.

Patients with Hepatic Impairment: — In a pharmacokinetic hepatic impairment (HI) study [see Use in Specific Populations (8.6)]:

Male and Female Patients: Males aged 20 to 34 years were shown to have had higher Cmax than females aged 20 to 27 years) while males aged 66 to 75 years had lower Cmax compared to females aged 66 to 74 years. The clinical significance of the findings is unknown.

Patients with Renal Impairment: The pharmacokinetics of cabergoline were not altered in 12 patients with moderate-to-severe renal impairment as assessed by creatinine clearance.