Cabergoline

Cabergoline Uses, Dosage, Side Effects, Food Interaction and all others data.

Cabergoline Tablet contains Cabergoline, a dopamine receptor agonist. Cabergoline is a dopaminergic ergoline derivative with potent and long-lasting prolactin lowering activity. It acts by direct stimulation of the D2-dopamine receptors on pituitary lactotrophs, thus inhibiting prolactin secretion.

Cabergoline stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors, which are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3 and D4 subreceptors, which are associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2 and D3 receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits: agonist activity (in order of decreasing binding affinities) on 5-hydroxytryptamine (5-HT)2B, 5-HT2A, 5-HT1D, dopamine D4, 5-HT1A, dopamine D1, 5-HT1B and 5-HT2C receptors and antagonist activity on α2B, α2A, and α2C receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2A agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion.

Trade Name Cabergoline
Availability Prescription only
Generic Cabergoline
Cabergoline Other Names Cabergolina, Cabergoline, Cabergolinum
Related Drugs bromocriptine, Dostinex, Parlodel, Permax, pergolide
Weight 0.5mg,
Type Oral tablet
Formula C26H37N5O2
Weight Average: 451.6043
Monoisotopic: 451.294725453
Protein binding

Moderately bound (40% to 42%) to human plasma proteins in a concentration-independent manner.

Groups Approved
Therapeutic Class Antiparkinson drugs
Manufacturer
Available Country United States, Netherlands
Last Updated: September 19, 2023 at 7:00 am
Cabergoline
Cabergoline

Uses

1. Cabergoline is used for the inhibition of physiological lactation soon after delivery, stillbirth, abortion or miscarriage.

2. Cabergoline is used for the treatment of dysfunctions associated with hyperprolactinaemia, including- amenorrhoea, oligomenorrhoea, anovulation and galactorrhoea. Cabergoline is used for patients with prolactin-secreting pituitary adenomas (micro- and macroprolactinomas), idiopathic hyperprolactinaemia, or empty sella syndrome with associated hyperprolactinaemia, which represent the basic underlying pathologies contributing to the above clinical manifestations.

Cabergoline is also used to associated treatment for these conditions: Idiopathic hyperprolactinemic disorder, Inhibition of physiological lactation

How Cabergoline works

The dopamine D2 receptor is a 7-transmembrane G-protein coupled receptor associated 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-gated 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 mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated 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.

Dosage

Cabergoline dosage

Cabergoline is to be administered by the oral route. It should be preferably taken with meals.

The recommended dosage of Cabergoline tablets for initiation of therapy is 0.25 mg twice a week. Dosage may be increased by 0.25 mg twice weekly up to a dosage of 1 mg twice a week according to the patient's serum prolactin level. Dosage increases should not occur more rapidly than every 4 weeks, so that the physician can assess the patient's response to each dosage level. If the patient does not respond adequately and no additional benefit is observed with higher doses, the lowest dose that achieved maximal response should be used and other therapeutic approaches considered. After a normal serum prolactin level has been maintained for 6 months, Cabergoline may be discontinued, with periodic monitoring of the serum prolactin level to determine whether or when treatment with Cabergoline should be reinstituted.

Inhibition of physiological lactation: Cabergoline should be administered during the first day after delivery. The recommended therapeutic dose is 1mg (two 0.5mg tablets) as a single dose.

To stop lactation once have started to breastfeed: 0.25 mg (one half of Cabergoline 0.5 mg tablet) every 12 hours for two days.

Treatment of hyperprolactinaemic disorders: The recommended initial dosage of Cabergoline is 0.5mg per week given in one or two (½ of a 0.5mg tablet) doses (e.g. on Monday and Thursday) per week. The weekly dose should be increased gradually preferably by adding 0.5mg per week at monthly intervals. The therapeutic dosage is usually 1mg per week and ranges from 0.25 to 2mg per week. Doses of Cabergoline up to 4.5mg per week have been used in hyperprolactinaemic patients until the optimal therapeutic response is achieved.

Severe hepatic insufficiency: Lower doses should be considered in patients with severe hepatic insufficiency.

Children: The safety and efficacy of Cabergoline has not been established in subjects less than 16 years of age.

Elderly: Data for use of Cabergoline in elderly is very limited. Available data do not indicate a special risk.

Side Effects

All side effects were mild to moderate in severity and of a transient nature. The most frequently occurring adverse events were dizziness/vertigo, headache, nausea and abdominal pain. In addition rarely palpitations, epigastric pain, somnolence, epistaxis and transient hemianopsia, vomiting, syncope, asthenia, and hot flushes were reported. Cabergoline withdrawal results in reversal of side effects, usually within a few days after discontinuation.

Asymptomatic decreases in blood pressure (20mmHg systolic and 10mmHg diastolic) may occur usually once during the first 3-4 days after child birth.

Toxicity

Overdosage might be expected to produce nasal congestion, syncope, or hallucinations.

Precaution

Hypersensitive (allergic) to Cabergoline, to other medicines called ergot alkaloids, (e.g. pergolide, bromocriptine, lisuride, ergotamine or ergometrine) or to any of the other ingredients in the tablet.

Severe liver disease and High blood pressure in pregnancy associated with swelling and protein in the urine.

Anti-psychotics or have a history of mental illness associated with child-birth.

Interaction

Cabergoline should not be administered concurrently with –D2 antagonists, such as Phenothiazines, Butyrophenones, Thioxanthenes, Or Metoclopramide.

Medicines to lower blood pressure. Medicines used to treat mental illness (e.g. antipsychotic medicines like chlorpromazine, haloperidol). Medicines for nausea and vomiting (e.g. domperidone). Medicines for severe migraine headaches (e.g. pergolide bromocriptine, lisuride, ergotamine, dihydroergotamine, ergometrine or methysergide).

Food Interaction

  • Exercise caution with grapefruit products. Cabergoline is partially metabolized through the CYP3A4 pathway. Therefore coadministration with grapefruit, a CYP3A4 inhibitor, may increase its serum concentration.
  • Exercise caution with St. John's Wort. Cabergoline is partially metabolized through the CYP3A4 pathway. Therefore coadministration with St. John's Wort, a CYP3A4 inducer, may reduce its serum concentration.
  • Take with or without food. Taking cabergoline with food may reduce gastric irritation.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Cabergoline Hypertension interaction

[Major] The use of cabergoline is contraindicated in patients with uncontrolled hypertension.

Cabergoline is a dopamine agonist and effects on alpha and

Elimination Route

First-pass effect is seen, however the absolute bioavailability is unknown.

Half Life

The elimination half-life is estimated from urinary data of 12 healthy subjects to range between 63 to 69 hours.

Clearance

  • renal cl=0,008 L/min
  • nonrenal cl=3.2 L/min

Elimination Route

After oral dosing of radioactive cabergoline to five 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.

Pregnancy & Breastfeeding use

Treated with Cabergoline for a long period and have or had fibrotic reactions (scar tissue) affecting your heart.

During pregnancy: Before Cabergoline administration, pregnancy should be excluded. Cabergoline should be used during pregnancy only if clearly needed. If conception occurs during therapy with Cabergoline, discontinuation of treatment should be considered, after careful evaluation of the risks and benefits to mother and foetus.

During lactation: No information is available on the excretion in breast milk in humans; however, mothers should be advised not to breast-feed in case of failed lactation inhibition/suppression by Cabergoline. Since it prevents lactation, Cabergoline should not be administered to mothers with hyperprolactinaemic disorders who wish to breast-feed their infants.

Contraindication

History of serious mental disease, particularly psychotic disorders. Liver or kidney disease n High blood pressure in pregnancy associated with swelling and protein in the urine (toxaemia of pregnancy). Anti-psychotics or have a history of mental illness associated with child-birth (puerperal psychosis).

Acute Overdose

There is no experience in humans of overdosage with Cabergoline in the proposed indications: it is likely to lead to symptoms due to over-stimulation of dopamine receptors.

These might include nausea, vomiting, gastric complaints, hypotension, nasal congestion, confusion hallucinations, psychosis or thought/perception disturbances. Treatment of overdose is symptomatic and supportive.

In addition, in case of pronounced central nervous system effects the administration of dopamine antagonist drugs may be advisable.

Storage Condition

Store in a cool & dry place, protected from light and moisture.

Keep out of reach of children.

Innovators Monograph

You find simplified version here Cabergoline

Cabergoline contains Cabergoline see full prescribing information from innovator Cabergoline Monograph, Cabergoline MSDS, Cabergoline FDA label

*** Taking medicines without doctor's advice can cause long-term problems.
Share