Cabergoline 0.5mg Tablets

Document: spc-doc_PL 00289-0988 change


Cabergoline 0.5 mg Tablets


Each tablet contains 0.5 mg cabergoline.

Excipient(s) with known effect: lactose 75.8 mg For the full list of excipients, see section 6.1.



White, oval-shaped, flat bevelled tablets. One side is smooth and the other side has a dividing score line and is debossed with ‘CBG’ and ‘0.5’ on either side of the score.

The tablet can be divided into equal doses.


4.1    Therapeutic indications

Inhibition of lactation for medical reasons.

Hyperprolactimaemic disorders Prolactin secreting pituitary adenomas Idiopathic hyperprolactinaemia

It is recommended that the medicinal product is initially prescribed by an appropriate specialist or after consulting a specialist.

4.2 Posology and method of administration



Treatment of hyperprolactinaemic disorders:

The recommended initial dosage is 0.5 mg cabergoline per week given in one or two doses (e.g. on Monday and Thursday) per week. The weekly dose should be increased gradually, preferably by adding 0.5 mg cabergoline per week at monthly intervals until an optimal therapeutic response is achieved.

The therapeutic dosage is usually 1 mg cabergoline per week and ranges from 0.25 mg to 2 mg cabergoline per week. Doses of up to 4.5 mg cabergoline per week have been used in hyperprolactinaemic patients.

The weekly dose may be given as a single administration or divided into two or more doses per week according to patient tolerability. Division of the weekly dose into multiple administrations is advised when doses higher than 1 mg cabergoline per week are to be given since the tolerability of doses greater than 1 mg cabergoline taken as a single weekly dose has been evaluated only in a few patients.

Patients should be evaluated during dose escalation to determine the lowest dosage that produces the therapeutic response.

For inhibition of lactation:

Cabergoline should be administered within the first 24 hours post-partum. The recommended therapeutic dosage is 1 mg cabergoline given as a single dose.

Patients with hepatic or renal impairment:

Use in patients with hepatic insufficiency and renal insufficiency see sections 4.3 and


Paediatric population:

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

Older people:

As a consequence of the indications for which cabergoline is presently proposed, the experience in elderly is very limited. Available data do not indicate a special risk.

Method of administration

Cabergoline is to be administered by the oral route.

In order to reduce the risk of gastrointestinal undesirable effects it is recommended that cabergoline is taken with meals for all therapeutic indications.

The maximum dose of 3mg/day of cabergoline must not be exceeded.

4.3. Contraindications

Pre-eclampsia, eclampsia

Post-partum hypertension or uncontrolled hypertension.

Hypersensitivity to the active substance, any ergot alkaloid or to any excipient listed in section 6.1.

Severe impairment of liver function

History of pulmonary, pericardial and retroperitoneal fibrotic disorders.

History of psychosis or risk of post-partum psychosis

For long-term treatment: evidence of cardiac valvulopathy as determined by pretreatment echocardiography (See section 4.4 Special warnings and precautions for use - Fibrosis and cardiac valvulopathy and possibly related clinical phenomena).

4.4 Special warnings and precautions for use


As with other ergot derivatives, cabergoline should be given with caution to subjects with severe cardiovascular disease, hypotension, Raynaud's syndrome, peptic ulcer or gastrointestinal bleeding, or with a history of serious, particularly psychotic, mental disorders.

The effects of alcohol on overall tolerability of cabergoline are currently unknown.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Hepatic insufficiency:

Lower doses should be considered in patients with severe hepatic insufficiency who receive prolonged treatment with cabergoline. Compared to normal volunteers and those with lesser degrees of hepatic insufficiency, an increase in AUC has been seen in patients with severe hepatic insufficiency (Child-Pugh Class C) who received a single 1 mg dose.

Postural hypotension:

Postural hypotension can occur following administration of cabergoline. Care should be exercised when administering cabergoline concomitantly with other drugs known to lower blood pressure.

Fibrosis and cardiac valvulopathy and possibly related clinical phenomena:

Fibrotic and serosal inflammatory disorders such as pleuritis, pleural effusion, pleural fibrosis, pulmonary fibrosis, pericarditis, pericardial effusion, cardiac valvulopathy involving one or more valves (aortic, mitral and tricuspid) or retroperitoneal fibrosis have occurred after prolonged usage of ergot derivatives with agonist activity at the serotonin 5HT2B receptor, such as cabergoline. In some cases, symptoms or manifestations of cardiac valvulopathy improved after discontinuation of cabergoline.

Erythrocyte sedimentation rate (ESR) has been found to be abnormally increased in association with pleural effusion/fibrosis. Chest x-ray examination is recommended in cases of unexplained ESR increases to abnormal values.

Valvulopathy has been associated with cumulative doses, therefore, patients should be treated with the lowest effective dose. At each visit, the risk benefit profile of cabergoline treatment for the patient should be reassessed to determine the suitability of continued treatment with cabergoline.

Before initiating long-treatment:

All patients should undergo a cardiovascular evaluation, including echocardiogram, to assess the potential presence of asymptomatic valvular disease. It is also appropriate to perform baseline investigations of erythrocyte sedimentation rate or other inflammatory markers, lung function/chest x-ray and renal function prior to initiation of therapy. In patients with valvular regurgitation, it is not known whether cabergoline treatment might worsen the underlying disease. If fibrotic valvular disease is detected, the patient should not be treated with cabergoline. (See Section 4.3 Contraindications).

During long-term treatment:

Fibrotic disorders can have an insidious onset and patients should be regularly monitored for possible manifestations of progressive fibrosis. Therefore during treatment, attention should be paid to the signs and symptoms of:

■    Pleuro-pulmonary disease, such as dyspnoea, shortness of breath, persistent cough, or chest pain.

■    Renal insufficiency or ureteral/abdominal vascular obstructions that may occur with pain in the loin/flank, and lower limb oedema, as well as any possible abdominal masses or tenderness that may indicate retroperitoneal fibrosis.

■    Cardiac failure; cases of valvular and pericardial fibrosis have often manifested as cardiac failure.

Therefore, valvular fibrosis (and constrictive pericarditis) should be excluded if such symptoms occur.

Clinical diagnostic monitoring for development of valvular disease or fibrotic disorders, as appropriate, is essential. Following treatment initiation, the first echocardiogram must occur within 3-6 months, thereafter, the frequency of echocardiographic monitoring should be determined by appropriate individual clinical assessment with particular emphasis on the above-mentioned signs and symptoms, but must occur at least every 6 to 12 months.

Cabergoline should be discontinued if an echocardiogram reveals new or worsened valvular regurgitation, valvular restriction or valve leaflet thickening (See Section 4.3 Contraindications).

The need for other clinical monitoring (e.g. physical examination including careful cardiac auscultation, X-ray, CT scan) should be determined on an individual basis.

Additional appropriate investigations such as erythrocyte sedimentation rate, and serum creatinine measurements should be performed if necessary to support a diagnosis of fibrotic disorder.

Somnolence/sudden sleep onset:

Cabergoline has been associated with somnolence. Dopamnie agonists can be associated with sudden sleep onset episodesin patients with Parkinson’s disease. A reduction of dosage or termination of treatment may be considered (See section 4.7 Effects on ability to drive and use machines).


Impulse control disorders

Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including cabergoline. Dose reduction/tapered discontinuation should be considered if such symptoms develop.

Inhibition/suppression of physiologic lactation:

As with other ergot derivatives, cabergoline should not be used in women with pregnancy-induced hypertension, for example, preeclampsia or post-partum hypertension, unless the potential benefit is judged to outweigh the possible risk.

A single dose of 0.25 mg of cabergoline should not be exceeded in nursing women treated for suppression of established lactation to avoid potential postural hypotension. (See section 4.2 Posology and method of administration -Inhibition/suppression of physiologic lactation and subsection above - Postural hypotension).

Treatment of hyperprolactinaemic disorders:

Because hyperprolactinaemia accompanied with amenorrhoea/galactorrhea and infertility may be associated with pituitary tumour, a complete evaluation of the pituitary is indicated before treatment with cabergoline is initiated.

Cabergoline restores ovulation and fertility in women with hyperprolactinemic hypogonadism.

Before administration of cabergoline, pregnancy should be excluded. Because clinical experience is still limited and the product has a long half-life, as a precautionary measure it is recommended that once regular ovulatory cycles have been achieved women seeking pregnancy discontinue cabergoline one month before intended conception.

Because pregnancy might occur prior to reinitiation of menses, a pregnancy test is recommended at least every 4 weeks during the amenorrheic period and, once menses are reinitiated, every time a menstrual period is delayed by more than 3 days. Women who wish to avoid pregnancy should be advised to use mechanical contraception during treatment with cabergoline and after discontinuation of cabergoline until recurrence of anovulation. As a precautionary measure, women who become pregnant should be monitored to detect signs of pituitary enlargement since expansion of preexisting pituitary tumors may occur during gestation

Renal insufficiency:

No overall differences in the pharmacokinetics of cabergoline were observed in moderate to severe renal disease. The pharmacokinetics of cabergoline has not been studied in patients having end-stage renal failure, or in patients on haemodialysis; these patients should be treated with caution.

4.5 Interaction with other medicinal products and other forms of interaction

No information is available about interaction between cabergoline and other ergot alkaloids; therefore, the concomitant use of these medications during long-term treatment with cabergoline is not recommended.

Since cabergoline exerts its therapeutic effect by direct stimulation of dopamine receptors, it should not be concurrently administered with drugs that have dopamine-antagonist activity (such as phenothiazines, butyrophenones, thioxanthenes, metoclopramide) since these might reduce the prolactin-lowering effect of cabergoline.

Concomitant use not recommended:

As with other ergot derivatives, cabergoline should not be used with macrolide antibiotics (e.g., erythromycin) due to increased systemic bioavailability of cabergoline.


Interactions with other medicinal products that reduce blood pressure should be taken into consideration.

No pharmacokinetic interactions with L-dopa or selegiline have been observed in studies of patients with Parkinson’s disease. Pharmacokinetic interactions with other medicinal products cannot be predicted based on available information about the metabolism of cabergoline.

4.6 Fertility, pregnancy and lactation


There are no adequate and well-controlled studies from the use of cabergoline in pregnant women. Animal studies have not demonstrated teratogenic effects, but reduced fertility and embryo-toxicity were observed in association with pharmacodynamic activity (see section 5.3).

In a twelve year observational study on pregnancy outcomes following cabergoline therapy, information is available on 256 pregnancies. Seventeen of these 256 pregnancies (6.6%) eventuated in major congenital malformations or abortion. Information is available on 23/258 infants who had a total of 27 neonatal abnormalities, both major and minor. Musculoskeletal malformations were the most common neonatal abormality (10), followed by cardio-pulmonary abnormalities (5). There is no information on perinatal disorders or long-term development of infants exposed to intra-uterine cabergoline. Based on recent published literature, the prevalence of major congenital malformations in the general population has been reported to be 6.9% or greater. Rates of congenital abnormality vary between different populations. It is not possible to accurately determine if there is an increased risk as no control group was included.

Cabergoline should only be used during pregnancy if clearly indicated and after an accurate benefit/risk evaluation. (See section “Special warning and precautions for use” - Treatment of Hyperprolactinemic Disorders)

Due to the long half-life of the drug and limited data on in utero exposure, women planning to become pregnant should discontinue cabergoline one month before intended conception. If conception occurs during therapy, treatment should be discontinued as soon as pregnancy is confirmed to limit foetal exposure to the drug. Contraception should be continued for at least 4 weeks after stopping cabergoline.


In rats, cabergoline and/or its metabolites are excreted in milk. 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 hyperprolactinemic disorders who wish to breast-feed their infants.


Cabergoline restores ovulation and fertility in women with hyperprolactinaemic hypogonadism: since pregnancy might occur prior to reinitiation of menses, pregnancy testing is recommended as appropriate during the amenorrhoeic period and, once menses are reinitiated, every time a menstrual period is delayed by more than three days. Women not seeking pregnancy should be advised to use effective nonhormonal contraception during treatment and after cabergoline withdrawal. Because of limited experience on the safety of foetal exposure to cabergoline, it is advisable that women seeking pregnancy conceive at least one month after cabergoline discontinuation. As a precautionary measure, women who become pregnant should be monitored to detect signs of pituitary enlargement since expansion of pre-existing pituitary tumours may occur during gestation.

4.7 Effects on ability to drive and use machines

Patients should be careful when performing actions which require fast and accurate reaction during treatment initiation.

Patients treated with cabergoline and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (eg, operating machines) until such episodes and somnolence have resolved (See section 4.4 Special warnings and precautions for use - Somnolence/sudden sleep onset).

4.8 Undesirable effects

The undesirable effects are usually dose-dependent, and can be reduced by decreasing the dose gradually.

Inhibition of lactation: Approximately 14% of the patients experience undesirable effects. The most common are low blood pressure (12%), dizziness (6%) and headaches (5%). Long-term treatment increases the frequency of undesirable effects to approximately 70%.

The following undesirable effects have been observed and reported during treatment with cabergoline with the following frequencies: very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

MedDRA System Organ Class


Undesirable Effects

Cardiac disorders

Very Common

Valvulopathy (including regurgitation) and related disorders (pericarditis and pericardial effusion)



Not Known

Angina pectoris

Respiratory, thoracic and mediastinal disorders


Dyspnoea, pleural effusion, fibrosis, (including pulmonary fibrosis), epistaxis

Very rare

Pleural fibrosis

Not Known

Respiratory disorder, respiratory failure, pleuritis, chest pain

Immune system disorders


Hypersensitivity reaction

MedDRA System Organ Class


Undesirable Effects

Nervous system disorders

Very common

Headache*, dizziness/vertigo*




Transient hemianopsia, syncope,

Not Known

Sudden sleep onset, tremor,

Eye disorders

Not Known

Visual impairment

Psychiatric disorders




Increased libido

Not Known

Aggression, delusions, hypersexuality, pathological gambling, psychotic disorder, hallucinations

Vascular disorders


Cabergoline generally exerts a hypotensive effect in patients on long-term treatment; Postural hypotension, hot flushes**


Digital vasospasm, fainting



Very common

Nausea*, dyspepsia, gastritis, abdominal


Constipation, vomiting**


Epigastric pain

General disorders and administration site conditions

Very Common

Asthenia***, fatigue


Oedema, peripheral oedema


Not Known

Hepatic function abnormal

Skin and

subcutaneous tissue disorders


Facial redness

MedDRA System Organ Class


Undesirable Effects


Rash, alopecia

Musculoskeletal and connective tissue


Leg cramps


Cramp in fingers

Reproductive system and breast disorders


Breast pain



Asymptomatic decreases in blood pressure (> 20 mmHg systolic and > 10 mmHg


A decrease in haemoglobin values have been observed in amenhorrheic women during the first few months after menses

Not Known

Blood creatinine phosphokinase increased, liver function tests abnormal

*Very common in patients treated for hyperprolactinaemin disorders; Common in patients treated for inhibition/supression of lactation

** Common in patients treated for hyperprolactinaemic disorders; Uncommon in patients treated for inhibition/supression of lactation

*** Very common in patients treated for hyperprolactinaemic disorders; Uncommon in patients treated for inhibition/supression of lactation

Impulse control disorders

Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including cabergoline (see section „Special warnings and precautions for use“).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal

product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at:

4.9 Overdose

Symptoms of overdose would likely be those of over-stimulation of dopamine receptors, eg, nausea, vomiting, gastric complaints, postural hypotension, confusion/psychosis or hallucinations.

Supportive measures should be taken to remove unabsorbed drug and maintain blood pressure, if necessary. In addition, the administration of dopamine antagonist drugs may be advisable.


5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Prolactin inhibitor ATC code: G02CB03

Cabergoline is a synthetic ergot alkaloid and an ergoline derivate with long-acting dopamine agonist and prolactin-inhibiting properties. A central dopaminergic effect via D2-

receptor stimulation is achieved through higher doses than doses that reduce the levels of serum prolactin.

The prolactin-reducing effect is dose-dependent, starting within 3 hours and remaining for 2-3 weeks. The long-acting effect means that a single dose is generally sufficient to stop the initiation of milk secretion. In treatment of hyperprolactinaemia, the serum prolactin levels are generally normalised within two to four weeks of the optimal dose being attained. Prolactin can still be significantly reduced several months after withdrawal of the treatment.

With regard to the endocrine effects of cabergoline not related to the antiprolactinaemic effect, available data from humans confirm the experimental findings in animals indicating that the test compound is endowed with a very selective action with no effect on basal secretion of other pituitary hormones or cortisol.

The pharmacodynamic actions of cabergoline not correlated with the therapeutic effect only relate to blood pressure decrease. The maximal hypotensive effect of cabergoline as single dose usually occurs during the first 6 hours after active substance intake and is dose-dependent both in terms of maximal decrease and frequency.

5.2 Pharmacokinetic properties


After oral administration cabergoline is rapidly absorbed from the gastrointestinal tract as the peak plasma concentration is received within 0.5 to 4 hours.

Food does not appear to affect absorption and disposition of cabergoline.


“In-vitro” experiments showed that cabergoline at concentrations of 0.1 - 10 ng/ml is 41-42% bound to plasma proteins.


In urine, the main metabolite identified is 6-allyl-8B-carboxy-ergoline, which accounts for 46% of the dose. Three additional metabolites are identified in urine, which account overall for less than 3% of the dose. The metabolites have been found to be much less potent than cabergoline in inhibiting prolactin secretion “in-vitro”.


The elimination half-life of cabergoline, is long; (63-68 hours in healthy volunteers and 79115 hours in hyperprolactinaemic patients.

On the basis of the elimination half-life, steady state conditions should be achieved after 4 weeks, as confirmed by the mean peak plasma levels of cabergoline obtained after a single dose (37 ± 8 pg/ml) and after a 4 week multiple-regimen (101 ± 43 pg/ml)-for 0.5mg cabergoline dose.

Ten days after administration about 18% and 72% of the dose is recovered in urine and faeces, respectively. Unchanged cabergoline in urine accounts for 2-3% of the dose.


The pharmacokinetic profile is linear up to 7 mg per day.

5.3 Preclinical safety data

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 postimplantation 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).


6.1 List of excipients

Anhydrous lactose L-Leucine

Magnesium stearate (E572)

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

2 years

6.4    Special precautions for storage

Do not store above 30°C. Store in the original package in order to protect from moisture. The drying capsule or bag with silica gel must not be removed from the bottle.

6.5 Nature and contents of container

Brown glass bottles (type III) containing a dessication capsule with silica gel with an induction-sealed childproof aluminium membrane and childproof HDPE top.


Brown glass bottles (type III) containing a dessication bag with silica gel with an induction-sealed childproof aluminium membrane and childproof PP top.

External box.

Packaging sizes: 2, 8, 14, 15, 16, 20, 28, 30, 32, 40, 48, 50, 60, 90, 98, 100 tablets. Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.


Teva UK Ltd.

East Sussex BN22 9AG United Kingdom


PL 00289/0988