Indication of Cabergoline

For the treatment of hyperprolactinemic disorders, either idiopathic or due to prolactinoma (prolactin-secreting adenomas). May also be used to manage symptoms of Parkinsonian Syndrome as monotherapy during initial symptomatic management or as an adjunct to levodopa therapy during advanced stages of disease. Also useUterine fibroids, Acromegaly, Cushing’s disease, Pituitary adenomas, Lactation suppression. 

Cabergoline Doses:

 Adult dose:

Oral 

Inhibition of physiological lactation: 1mg as a single dose on the 1st day postpartum.

Suppression of lactation: 250 mcg every 12 hr for 2 days.

Hyperprolactinaemia-associated disorders: Initially, 500mcg/week than increased at monthly intervals by 500 mcg/week according to response. Weekly dose may be admin on a single occasion or in 2 divided doses on separate days, doses >1 mg should be given as divided doses. Usual dose: 1 mg ( up to 4.5 mg )/week.

As monotherapy in Parkinson’s disease; Adjunct to levodopa treatment in parkinson’s disease.

Initialy, 0.5 mg daily in monotherapy and 1 mg daily as adjunct, may increase in increments of 0.5 – 1 mg at 7 or 14 day intervals. Max: 3 mg daily.

Elder: Start with lower doses.

Child doses:

Safety and Efficacy has not been established.

Administration

Should be taken with food.

Contraindications

Hypersensitivity to ergot derivatives. Uncontrolled hypertension.

Cabergoline Side effects

Common side effects

Nausea, vomiting, heartburn, constipation, tiredness, dizziness, breast pain, painful menstrual periods, burning, numbness, or tingling in the arms, hands, legs, or feet.

Serious side effects

Shortness of breath, difficulty breathing when lying down, cough, chest pain, swelling of the hands, feet, ankles, or lower legs, decrease in urination, pain in the back, side, or groin, lumps or pain in the stomach area, abnormal vision.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Precautions and Warnings

CV disease, Raynaud’s syndrome, Renal or hepatic impairment, Peptic ulcer, GI bleeding, History of psychosis, Hypertension, May affect abilityto drive or operate machinery. Pregnancy, Lactation. Prolonged use and/or usege of high doses may lead to psychiatric disorders, Pleural/ retroperitoneal fibrosis or cardiac valvular fibrosis. Monitor serum prolactin level monthly until normalisation. Monitor hepatic function regularly in patients with hepatic impairment.

Lactation: Excretion in milk unknown, use with caution.

Pregnancy and Lactation

Pregnancy category – B

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women or animel studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester

Lactation: Excretion in milk unknown; not recommended.

Therapeutic class

Drugs for milk suppression, Anti-parkinson drugs.

Description of Cabergoline

DOSTINEX Tablets contain cabergoline, a dopamine receptor agonist. The chemical name for cabergoline is 1-[(6-allylergolin-8β-yl)- carbonyl]-1-[3-(dimethylamino) propyl]-3-ethylurea. Its empirical formula is C26H37N5O2 and its molecular weight is 451.62. The structural formula is as follows:

DOSTINEX® cabergoline Structural Formula Illustration

Cabergoline is a white powder soluble in ethyl alcohol, chloroform, and N, N-dimethylformamide (DMF); slightly soluble in 0.1N hydrochloric acid; very slightly soluble in n-hexane; and insoluble in water.

DOSTINEX Tablets, for oral administration, contain 0.5 mg of cabergoline. Inactive ingredients consist of leucine, USP, and lactose, NF.

Cabergoline Mode of Action

The dopamine D2 receptor is a 7-transmembrane G-protein couple receptor associate with Gi proteins. In lactotrophs, stimulation of dopamine D2 causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP3-dependent release of Ca2+ from intracellular stores.

Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gate calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p42/p44 MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediate by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediate by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition.

Stimulation of dopamine D2 receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders. Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors. Receptor-binding studies indicate that cabergoline has low affinity for dopamine D1, α1,- and α2- adrenergic, and 5-HT1- and 5-HT2-serotonin receptors.

Drug Interaction

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug include: antipsychotic medications (such as chlorpromazine, haloperidol, thiothixene), lorcaserin, metoclopramide, prochlorperazine.

Other medications can affect the removal of cabergoline from your body, which may affect how cabergoline works. Examples include certain azole antifungals (such as itraconazole, ketoconazole, posaconazole), cobicistat, HIV protease inhibitors (such as saquinavir), ritonavir, among others.