CABERGOLIN TABLET

NAME OF THE MEDICINAL PRODUCT

Cabergolin Tablet 0.5 mg IP

Cabergolin Tablet 0.25 mg USP,

Cabergolin Tablet 0.5 mg USP

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains contains 0.5 mg cabergoline.
Excipients with known effect:
Each tablet contains 75.90 mg of lactose.

PHARMACEUTICAL FORM
Tablet. Flat, capsule-shaped, 4 x 8 mm, scored, white tablets.

CLINICAL PARTICULARS

Therapeutic indications
Inhibition/suppression of physiological lactation

Cabergoline is indicated for the inhibition of physiological lactation soon after delivery and for suppression of already established lactation:
1. After parturition, when the mother elects not to breast feed the infant or when breast feeding is contraindicated due to medical reasons related to the mother or the new-born.
2. After stillbirth or abortion.

Cabergoline prevents/suppresses physiological lactation by inhibiting prolactin secretion.

In controlled clinical trials, cabergoline given as a single 1 mg administration during the first day post-partum, was effective in inhibiting milk secretion, as well as breast engorgement and pain in 70 – 90% of the women. Less than 5% of women experienced rebound breast symptomatology during the third post-partum week (which was usually mild in severity).

Suppression of milk secretion and relief of breast engorgement and pain are obtained in approximately 85% of nursing women treated with a total dose of 1 mg cabergoline given in four divided doses over two days. Rebound breast symptomatology after day 10 is uncommon (approximately 2% of cases).

Treatment of hyperprolactinaemic disorders
Cabergoline is indicated for the treatment of dysfunctions associated with hyperprolactinaemia, including amenorrhoea, oligomenorrhoea, anovulation and galactorrhoea. Cabergoline is indicated in 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.

On chronic therapy, cabergoline at doses ranging between 1 and 2 mg per week, was effective in normalising serum prolactin levels in approximately 84% of hyperprolactinaemic patients. Regular cycles were resumed in 83% of previously amennorhoeic women. Restoration of ovulation was documented in 89% of women with progesterone levels monitored during the luteal phase. Galactorrhoea disappeared in 90% of cases showing this symptom before therapy. Reduction in tumour size was obtained in 50 – 90% of female and male patients with micro- or macroprolactinoma.

Posology and method of administration

Cabergoline is to be administered by the oral route. Since in clinical studies cabergoline has been mainly administered with food and since the tolerability of this class of compounds is improved with food, it is recommended that cabergoline be preferably taken with meals for all the therapeutic indications.

Inhibition/suppression of physiological lactation

For inhibition of lactation cabergoline should be administered during the first day post-partum. The recommended therapeutic dose is 1 mg (two 0.5 mg tablets) given as a single dose.

For suppression of established lactation the recommended therapeutic dosage regimen is 0.25 mg (one-half 0.5 mg tablet) every 12 hours for two days (1 mg total dose). This dosage regimen has been demonstrated to be better tolerated than the single dose regimen in women electing to suppress lactation having a lower incidence of adverse events, in particular of hypotensive symptoms.

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

The maximum dose should not exceed 3mg per day.

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 per week are to be given since the tolerability of doses greater than 1 mg 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. Monitoring of serum prolactin levels at monthly intervals is advised since, once the effective therapeutic dosage regimen has been reached, serum prolactin normalisation is usually observed within two to four weeks.
After cabergoline withdrawal, recurrence of hyperprolactinaemia is usually observed. However, persistent suppression of prolactin levels has been observed for several months in some patients. Of the group of women followed up, 23/29 had ovulatory cycles which continued for greater than 6 months after cabergoline discontinuation.

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

Use in the elderly
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.

CONTRAINDICATION
Hypersensitivity to cabergoline, any of the excipients listed in section 6.1 or any ergot alkaloid.

History of pulmonary, pericardial and retroperitoneal fibrotic disorders.

Cabergoline is contraindicated in patients with hepatic insufficiency and with toxaemia of pregnancy. Cabergoline should not be co-administered with anti-psychotic medications or administered to women with a history of puerperal psychosis.

For long-term treatment: Evidence of cardiac valvulopathy as determined by pre-treatment echocardiography.

SPECIAL PRECAUTIONS & WARNINGS
General:

The safety and efficacy of cabergoline have not yet been established in patients with renal and hepatic disease. As with other ergot derivatives, cabergoline should be given with caution to patients with severe cardiovascular disease, Raynaud’s syndrome, renal insufficiency, peptic ulcer or gastrointestinal bleeding, or with a history of serious, particularly psychotic, mental disorders. Particular care should be taken when patients are taking concomitant psychoactive medication.

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

Symptomatic hypotension can occur with cabergoline administration for any indication. Care should be exercised when administering cabergoline concomitantly with other drugs known to lower blood pressure.

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

Before cabergoline administration, pregnancy should be excluded and after treatment pregnancy should be prevented for at least one month.

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.

Somnolence/Sudden Sleep Onset:

Cabergoline has been associated with somnolence. Dopamine agonists can be associated with sudden sleep onset episodes in patients with Parkinson’s disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with cabergoline. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore a reduction in dosage or termination of therapy may be considered. (See section 4.7)

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 Dostinex. Dose reduction/tapered discontinuation should be considered if such symptoms develop.

Inhibition/suppression of physiological 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.

In post-partum studies with cabergoline, blood pressure decreases were mostly asymptomatic and were frequently observed on a single occasion 2 to 4 days after treatment. Since decreases in blood pressure are frequently noted during the puerperium, independently of drug therapy, it is likely that many of the observed decreases in blood pressure after cabergoline administration were not drug-induced. However, periodic monitoring of blood pressure, particularly during the first few days after cabergoline administration, is advised.

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). A clinical study exploring the efficacy and tolerability of 0.5 mg of cabergoline given as a single dose for suppression of lactation has shown that the risk of side effects is approximately doubled in this indication if the drug is administered as a single dose of 0.5 mg.

Treatment of hyperprolactinaemic disorders:

Because hyperprolactinaemia accompanied with amenorrhoea/galactorrhoea 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 hyperprolactinaemic hypogonadism.

Because pregnancy might occur prior to reinitiation of menses, a pregnancy test is recommended at least every four weeks during the amenorrhoeic period and, once menses are reinitiated, every time a menstrual period is delayed by more than three 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 pre-existing pituitary tumours may occur during gestation.

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. Should pregnancy occur during treatment, cabergoline is to be discontinued. 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.

Regular gynaecological assessment, including cervical and endometrial cytology, is recommended for patients taking cabergoline for extensive periods.

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-term treatment:

All patients must 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).

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 obstruction 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 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).

The need for other clinical monitoring (e.g. physical examination including, 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 a fibrotic disorder.

Interaction with other medicinal products and other forms of interaction

None stated.

Fertility, pregnancy and lactation
Megestrol Acetate is not recommended for women who are pregnant or who are breast feeding.
Several reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and genital abnormalities in male and female foetuses. The risk of hypospadias, 5 to 8 per 1,000 male births in the general population, may be approximately doubled with the exposure to progestational drugs. There are insufficient data to quantify the risk to exposed female foetuses, however some of these drugs induce mild virilisation of the external genitalia of the female foetuses.
If a patient is exposed to Megestrol Acetate during the first four months of pregnancy or if she becomes pregnant whilst taking Megestrol Acetate, she should be apprised of the potential risks to the foetus.
Women of child bearing potential should be advised to avoid becoming pregnant.

Breastfeeding
Because of the potential for adverse effects, nursing should be discontinued during treatment with Megestrol Acetate.

Effects on ability to drive and use machines
There are no known effects of megestrol acetate on the ability to drive or operate machinery.

UNDESIRABLE EFFECTS
The main side-effect experienced by patients while taking megestrol acetate, particularly at high doses, is weight gain, which is usually not associated with water retention, but which is secondary to an increased appetite and food intake. Weight gain is associated with an increase in fat and body cell mass.
Constipation and urinary frequency have also been reported in patients who received high doses of megestrol acetate in clinical trials.
A rarely encountered side effect of prolonged administration of megestrol acetate is urticaria, presumably an idiosyncratic reaction to the drug. The drug is devoid of the myelosuppressive activity characteristic of many cytotoxic drugs and it causes no significant changes in haematology, blood chemistry or urinalysis.

Pituitary adrenal axis abnormalities including glucose intolerance, new onset diabetes, exacerbation of pre-existing diabetes with decreased glucose tolerance and Cushing’s syndrome have been reported with the use of megestrol acetate. Clinically apparent adrenal insufficiency has been rarely reported in patients shortly after discontinuing megestrol acetate. The possibility of adrenal suppression should be considered in all patients taking or withdrawing from chronic megestrol acetate therapy. Replacement stress doses of glucocorticoids may be indicated.

The list is presented by system organ class, MedDRA preferred term, and frequency using the following frequency categories: very common (≥1/10), common (≥1/100, < 1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (< 1/10000), and not known (cannot be estimated from the available data).

System Organ Class Frequency MedDRA Term
Neoplasms benign, malignant, and unspecified (including cysts and polyps) Common Tumour flare #
Endocrine disorders Very common Adrenal insufficiency, cushingoid, Cushing’s syndrome
Metabolism and nutrition disorders Very common Diabetes mellitus, glucose tolerance impaired, hyperglycaemia, increased appetite
Psychiatric disorders Common Mood altered
Nervous system disorders Common Carpal tunnel syndrome, lethargy
Cardiac disorders Common Cardiac failure
Vascular disorders Very common Thrombophlebitis, pulmonary embolism*, hypertension, hot flush
Respiratory, thoracic and mediastinal disorders Very common Dyspnoea
Gastrointestinal disorders Common Nausea, vomiting, diarrhoea, flatulence
Very common Constipation
Skin and subcutaneous tissue disorders Common Rash, alopecia
Renal and urinary disorders Common Pollakiuria
Reproductive system and breast disorders Common Menrorrhagia, erectile dysfunction
General disorders and administration site condition Common Asthenia, pain, oedema
Investigations Very common Weight increased

Pharmacological particulars

Reports of overdose have also been received in the postmarketing setting. Signs and symptoms reported in the context of overdose included diarrhoea, nausea, abdominal pain, shortness of breath, cough, unsteady gait, listlessness, and chest pain. There is no specific antidote for overdose with Megestrol Acetate. In case of overdose, appropriate supportive measures should be taken.

Overdose
No acute toxicological effects have resulted from studies involving Megestrol Acetate (megestrol acetate) administered in dosages               as high as 1600 mg/day for six months or more.

Pharmacodynamic properties

megestrol acetate possesses pharmacological properties similar to those of natural progesterone. Its progestational activity is slightly greater than that of medroxyprogesterone acetate, norethindrone, norethindrone acetate and norethynodrel; slightly less than that of chlormadinone acetate; and substantially less than that of norgestrel.

Megestrol acetate is a potent progestogen that exerts significant anti-oestrogenic effects. It has no androgenic or oestrogenic properties. It has anti-gonadotropic, anti-uterotropic and anti-androgenic/anti-myotropic actions. It has a slight but significant glucocorticoid effect and a very slight mineralocorticoid effect.

 Pharmacokinetic properties

Orally Peak plasma levels of tritiated megestrol acetate and metabolites occur one to three hours after oral administration. When 4 to 91mg of c-labelled megestrol acetate were administered orally to women, the major route of drug elimination was in the urine. The urinary and fecal recovery of total radioactivity within 10 days ranged from 56.6% to 78.4% (mean 66.4%) and 7.7% to 30.3% (mean 19.8%), respectively. The total recovered radioactivity varied between 83.1% and 94.7% (mean 86.2%).

Megestrol acetate metabolites, which were identified in the urine as glucuronide conjugates, were 17-alpha-acetoxy-2-alpha hydroxy-6-methylpregna-4, 6-diene-3, 20-dione; 17-alpha-acetoxy-6-hydroxymethylpregna-4, 6-diene-3, 20-dione; and 17-alpha-acetoxy-2 alpha-hydroxy-6-hydromethylpregna-4, 6-diene-3, 20-dione; these identified metabolites accounted for only 5-8% of the administered dose.

Serum concentrations were measured after the administration of single and multiple oral doses of megestrol acetate. Adult male and post-menopausal female volunteers, no more than 65 years of age participated in the study.

Megestrol acetate is readily absorbed following oral administration of 20, 40, 80 and 200 mg doses. Megestrol serum concentrations increase with increasing doses, the relationship between increasing dosage and increasing serum levels not being arithmetically proportional. Average peak serum concentrations for the four doses tested were 89, 190, 209 and 465 ng/ml.

Mean peak serum concentrations are found three hours after single-dose administration for all dosage levels studied. The serum concentration curve appears biphasic, and the beta-phase half-life is 15 to 20 hours long.

After multiple doses over a three-day period, serum levels increase each day and are estimated to reach 80% to 90% predicted steady-state levels on the third day.

Preclinical safety data

Administration of megestrol acetate to female dogs for up to 7 years was associated with an increased incidence of both benign and malignant tumors of the breast. Comparable studies in rats and studies in monkeys were not associated with an increased incidence of tumors. The relationship of megestrol acetate-associated dog tumors to humans is unknown, but should be considered in assessing the benefit-to-risk ratio when prescribing Megestrol Acetate, and in surveillance of patients on therapy

Fertility and reproduction studies with high doses of megestrol acetate have shown a reversible feminising effect on some male rat foetuses.

Pharmaceutical particulars

List of excipients
Colloidal anhydrous silica
Lactose monohydrate
Magnesium stearate
Microcrystalline cellulose
Povidone
Sodium starch glycollate

 Incompatibilities

Not applicable.

 Shelf life

36 months – Blister packs
36 months – Amber glass bottles

.Special precautions for storage

Do not store Megestrol Acetate Tablets above 25°C. Store in the original package in order to protect from moisture.

 Nature and contents of container

Amber glass bottles of 30, 60 or 100

Blister packs of 30 tablets

Pack sizes: 30 and 100 tablets.

 Special precautions for disposal and other handling

None.

MARKETING AUTHORISATION HOLDER

TAJ PHARMA CIS LTD.
Marksistsky lane 6, office 221, Moscow, 109147, Russia

MANUFACTURER:

Manufactured in India by:
TAJ PHARMACEUTICALS LTD,
220, Mahagujarat Ind. Estate,  Moraiya,

Tal. Sanand , Dist. Ahmedabad,

Gujarat, INDIA.

Package leaflet:

Information for the patient

Cabergolin 0.5mg tablet

Your medicine is known by the above name, but will be referred to as Cabergoline throughout the following

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
– Keep this leaflet. You may need to read it again.
 – If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet
1) What Cabergoline is and what it is used for
2) What you need to know before you take Cabergoline
3) How to take Cabergoline
4) Possible side effects
5) How to store Cabergoline
6) Contents of the pack and other information

1.What Cabergoline is and what it is used for
Cabergoline belongs to a group of medicines known as prolactin inhibitors. Cabergoline prevents lactation (production of milk) by decreasing levels of a hormone known as prolactin. Cabergoline can also be used to reduce abnormal quantities of the hormone prolactin in the blood

2) What you need to know before you take Cabergoline

Do not take Cabergoline if you:
• are allergic to cabergoline or other ergot alkaloids (e.g. bromocriptine), or to any of the other ingredients of this medicine
• have (or have had in the past) psychosis or you are at risk of psychosis after childbirth
• have severely impaired liver function
• have swelling of the hands, feet and a high blood pressure during pregnancy (pre-eclampsia, eclampsia)
• have uncontrolled high blood pressure or high blood pressure after childbirth
• are pregnant or breast-feeding
• have previously experienced side effects affecting lung, such as fibrosis, associated with the use of dopamine agonists (e.g. bromocriptine, pergolide)
• will be treated with Cabergoline for a long period and have or had fibrotic reactions (scar tissue) affecting your heart.

Warnings and precautions
If you have any of the following health problems you must inform your doctor before taking Cabergoline as the medicinal product may be unsuitable for you:
• cardiovascular disease
• stomach ulcer or bleeding in the gastrointestinal tract, (this condition can cause black faeces or vomiting with blood)
• impaired kidney function
• liver or kidney disease
• history of serious mental disease, particularly psychotic disorders
• Raynaud’s disease (when it is cold the fingers and toes become bluish white, with no pulse, cold, insensitive and numb)
• low blood pressure or you are taking medicines to lower blood pressure
• increased blood pressure after giving birth
• serious chest complaint (e.g. pain in the chest when breathing, fluid in the lungs, inflammation or infection of the lungs)
• if you have ever been diagnosed in the past with a problem known as fibrotic disease (scar tissue) affecting the lungs, lower back and kidneys or heart.
In case you are treated with Cabergoline for a long period, your doctor will check before starting treatment whether your heart, lungs and kidneys are in a good condition. He/she will also have an echocardiogram (an ultrasound test of the heart) taken before treatment is started and at regular intervals during treatment. If fibrotic reactions occur, treatment will have to be discontinued.
Tell your doctor if you or your family/carer notices that you are developing urges or cravings to behave in ways that are unusual for you and you cannot resist the impulse, drive or temptation to carry out certain activities that could harm yourself or others. These are called impulse control disorders and can include behaviours such as addictive gambling, excessive eating or spending, an abnormally high sex drive or an increase in sexual thoughts or feelings.

Your doctor may need to adjust or stop your dose.
The effect of alcohol on the tolerability of cabergoline is unknown.
Infertility can be reversed in women taking Cabergoline, and pregnancy can occur before the menstrual cycle has normalised. Suitable means of contraception should therefore be used during treatment if necessary.
It is recommended that women on long term treatment with Cabergoline for hormonal disorders should have regular gynaecological exams including smear tests. Your doctor will continue to monitor your medical condition while you are taking Cabergoline tablets.

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

Other medicines and Cabergoline
• Certain medicines used for reducing blood pressure and certain medicinal products (e.g. phenothiazines, butyrophenones, thioxanthene) used for the treatment of psychological illnesses (schizophrenia or psychoses), if taken at the same time as Cabergoline, can interfere with the effects of cabergoline. The treating doctor should therefore be aware of such simultaneous medication.
• There are other medicines such as other ergot alkaloids, medicines to prevent vomiting (metoclopramide), medicines for reducing high blood pressure, and macrolide antibiotics (such as erythromycin) that may affect the activity and tolerability of Cabergoline. Tell your doctor or pharmacist if you are taking or have recently taken any other medicinal products, including those obtained without a prescription and natural medical products/natural products.

Cabergoline with food and drink
• Cabergoline should be taken by mouth, preferably with meals.

Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
 • There is only limited experience of the use of Cabergoline during pregnancy. You should therefore consult your doctor if you are pregnant or plan to become pregnant before the treatment is started.
• If you are being treated with Cabergoline and become pregnant during this time you should discontinue the treatment and contact your doctor as soon as possible
• Contraception should be continued for at least 4 weeks after stopping Cabergoline.

Breast-feeding
• It is not known whether cabergoline passes into breast milk
• Cabergoline should not be taken by mothers who intend to breast-feed as it prevents lactation. Nursing mothers should note that the quantity of milk can diminish.

Fertility
• If you are planning to become pregnant the Cabergoline should be discontinued one month before intended pregnancy. You should therefore consult your doctor if you are pregnant or plan to become pregnant before the treatment is started.

 Driving and using machines
• Cabergoline can negatively affect the ability to react in some people and this should be considered in cases where a high level of alertness is required, e.g. driving a car and in precision work
• Cabergoline can cause somnolence (extreme drowsiness) and sudden sleep onset. Persons affected by this should therefore not drive or take part in activities in which reduced alertness could incur a risk of serious harm (e.g. using machines), until such recurrent episodes and somnolence have resolved.

Cabergoline contains lactose
• Cabergoline 0.5mg tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars you should contact your doctor before taking this medicine.

3) How to take Cabergoline

  • Always take Cabergoline exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
    The dose is determined by your doctor who adjusts it individually for you. The tablets should be taken with meals to reduce certain side effects such as nausea, vomiting and stomach pains.
    To stop the production of breast milk:
    The usual dose is 1 mg (as a single dose) within 24 hours after giving birth• To reduce the concentration of prolactin in the body:
    Usually the treatment is started with 0.5 mg per week, but higher doses may then be necessary. Your doctor will tell you for how long you must take your tablets.
    Cabergoline 0.5mg Tablets have a score and can be divided into two equal halves. When you first start taking the tablet, it is recommended you slowly change position when trying to sit, stand or lie down, this is because Cabergoline may cause a drop in blood pressure that could make you dizzy when you move from a position. It is also recommended that you avoid alcohol and other medicines that cause drowsiness as this could increase the risk of dizziness. During treatment your doctor may need to check your blood pressure, particularly in the first few days of treatment. A gynaecological assessment may also be carried out on the cells of your cervix or womb lining.
    If you take more Cabergoline than you should

    It is important not to take too many tablets. Contact your nearest hospital Accident and Emergency department or a doctor for advice if you have taken too many tablets or if you think a child has swallowed any. Symptoms of overdose may include nausea, vomiting, reduced blood pressure, stomach pain, changes in behaviour, confusion or hallucinations (seeing things). Take this leaflet and any tablets that you still have to show the doctor.
    If you forget to take Cabergoline
     If you forget to take a dose at the right time, you can take it as soon as you remember it. If it is almost time to take the next dose, skip the forgotten dose and take the next dose as usual.
    If you stop using Cabergoline
    If you stop using Cabergoline the symptoms of your illness may become more severe and you should discuss with your doctor before you discontinue therapy. Cabergoline takes many days to be cleared from the bloodstream and effects may worsen over a 2 week period resulting in increased lactation.
    If you have any other questions on the use of this medicine, ask your doctor or pharmacist.

4) Possible side effects
Like all medicines, this medicine can cause side effects, although not everyone gets them.
When used for stopping the production of breast milk approximately 14 in 100 patients have some form of side effects. The most common are low blood pressure, dizziness and headache. In treatment of increased prolactin levels side effects are more common as the tablets are taken for a longer period of time. Approximately 70 in 100 patients then experience side effects, but the side effects mostly disappear or decrease after approx. 2 weeks.

Tell your doctor immediately if you experience any of the following symptoms after taking this medicine. These symptoms can be severe:
• abnormal or unusual thoughts
• heart valve and related disorders e.g. inflammation (pericarditis) or leaking of fluid in the pericardium (pericardial effusion). This is a very common side effect (may affect more than 1 in 10 patients). The early symptoms may be one or more of the following: difficulty breathing, shortness of breath, pounding heart, feeling faint, chest pain, back pain, pelvic pain or swollen legs. These may be the first signs of a condition called pulmonary fibrosis, which can affect the lungs, heart/heart valves or lower back.
• development of a widespread itchy rash, difficulty breathing with or without wheezing, feeling faint, unexplained swelling of the body or tongue or any other symptoms which appear to come on rapidly after taking this medication and make you feel unwell. These may be indicative of an allergic reaction. This is an uncommon side effect (may affect 1 to 10 users in 1000).

You may experience the following side effects: Inability to resist the impulse, drive or temptation to perform an action that could be harmful to you or others, which may include:
• Strong impulse to gamble excessively despite serious personal or family consequences
• Altered or increased sexual interest and behaviour of significant concern to you or to others, for example, an increased sexual drive
• Uncontrollable excessive shopping or spending • Binge eating (eating large amounts of food in a short time period) or compulsive eating (eating more food than normal and more than is needed to satisfy your hunger).

Tell your doctor if you experience any of these behaviours; they will discuss ways of managing or reducing the symptoms.
During treatment you may also notice the following side effects:


 Very common side effects (may affect more than 1 user in 10):
• Dizziness or spinning feeling (vertigo), headache, feeling sick (nausea), stomach pain, upset stomach, inflammation of the stomach lining (gastritis), feeling weak, tired or fatigued.

Common side effects (may affect 1 to 10 users in 100):
• low blood pressure upon standing (which can result in dizziness), depression, excessive daytime sleepiness, blurred vision, being sick (vomiting), constipation, breast pain, hot flushes, redness of the face, low blood pressure after childbirth which may not have any symptoms, low blood pressure (long term treatment).

Uncommon side effects (may affect 1 to 10 users in 1000):
• nosebleeds, leg cramps, fainting, your fingers or toes turn white or blue with a feeling of numbness after exposure to cold (digital vasospasm), crawling/prickling sensations in the body, loss of half of the vision in one or both eyes, pounding of the heart (palpitations), rash, hair loss, increased sex drive, swelling due to accumulation of fluid in the tissue (oedema), low haemoglobin values in blood, lung scar tissue, fluid in the space around the lung (pleural effusion).

 Rare side effects (may affect 1 to 10 users in 10,000):
• pain in the upper central abdomen
• cramps in fingers.

Not known (cannot be estimated from the available data):
• sudden sleep attacks, seeing and hearing things that are not real (hallucinations), delusions, psychotic disorder, unintentional trembling or shaking movements (tremor), chest pain (angina), abnormal liver and abnormal blood tests of liver function, breathing problems with inadequate intake of oxygen, inflammation of the lining of the lung (pleuritis), an increase in the level of some enzymes in the blood, loss of vision and aggression.
Development of excess fibrous connective tissue (fibrosis) e.g. in the heart, lungs and kidneys has been reported. You should become aware of this as difficulty breathing, chest pain, back pain and swelling of the legs. Cabergoline has been linked with somnolence and sudden sleep attacks.

Reporting of side effects:
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5) How to store Cabergoline

  • Keep all medicines out of the sight and reach of children.
    • Do not use cabergoline after the expiry date which is printed on the carton or the bottle label after EXP: The expiry date refers to the last day of that month.
    • Do not store above 25°C. Store in the original package in order to protect from moisture. The drying bag with silica gel must not be removed from the bottle.
    • If the tablets become discoloured or show any other signs of deterioration, you should seek the advice of your pharmacist who will tell you what to do.
    • Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment
  1. Further Information

What Cabergoline contains
• The active substance is Cabergoline. Each tablet contains 0.5mg cabergoline.
• The other ingredients are anhydrous lactose, L-leucine and magnesium stearate.

 

What Cabergoline looks like and the contents of the pack
White, oval, flat tablets with bevelled edges. 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. Each amber glass bottle contains 8 tablets with a tamper evident, child-resistant screw cap which contain silica gel desiccant. PL 10383/2123 Cabergoline 0.5mg Tablets

Manufactured by:
Taj Pharmaceuticals Limited
220, Mahagujarat Ind. Estate, Moraiya, Tal. Sanand, Dist. Ahmedabad, Gujarat, INDIA

Marketing Authorization Holder:
Regal sun co., Ltd.Myanmar

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