Kaberlin 0,5

General characteristics. Structure:

Active ingredient: 0,5 mg of a kabergolin in each tablet.

Auxiliary a veshchestva:tsellyuloza microcrystallic (avitset PH 200), a L-leucine.

Pharmacological properties:

Pharmacodynamics. Kabergolin – derivative ergot alkaloids, an agonist dopamine D2 receptors. Stimulates dopamine D2 receptors owing to what causes the expressed and long oppression of secretion of an anterior pituitary hormone – prolactin.

Kabergolin has low affinity to dopamine D1 receptors, a-1-, a-2 to adrenergic receptors, 5-HT1-and to 5HT2-serotoninovy receptors.

Kabergolin has therapeutic effect at a giperprolaktinemiya, reducing expressiveness of its such manifestations as disturbances of a menstrual cycle (an oligomenorrhea, an amenorrhea), infertility, a galactorrhoea, impotence, decrease in a libido. Prevents and suppresses a physiological lactation.

Prolaktinsnizhayushchy action is dozozavisimy as concerning expressiveness, and duration of action of a kabergolin.

Kabergolin possesses selective effect and does not exert impact on basal secretion of other hormones of a hypophysis, and also cortisol.

Pharmacokinetics. After oral administration каберголин it is quickly absorbed from digestive tract. Cmax in a blood plasma is reached in 0,5-4 hours. Meal does not influence absorption and distribution of a kabergolin.

Decrease in concentration of prolactin is noted in 3 hours after reception of a kabergolin and remains within 7-28 days at patients with a giperprolaktinemiya and 14-21 days – at suppression of a puerperal lactation.

Drug is intensively distributed in an organism. Kabergolin moderately contacts (from 40% to 42%) proteins of a blood plasma irrespective of concentration. The concomitant use of drugs with high communication with proteins does not influence the maintenance of a kabergolin.

Kabergolin is intensively metabolized. The key product of metabolism of a kabergolin identified in urine is 6-аллил-8β-карбокси-эрголин in concentration to 4–6% of the accepted dose. Content in urine of 3 additional metabolites does not exceed 3% of the accepted dose. Products of metabolism have considerably smaller effect concerning suppression of secretion of prolactin in comparison with kabergoliny. Participation of P450 cytochrome in metabolism minimum.

Т½, estimated on allocation speed with urine, makes 79-115 hours at patients with a giperprolaktinemiya.

Indications to use:

Inhibition/suppression of a physiological lactation. Inhibition of a physiological puerperal lactation right after childbirth or for suppression of the lactation which was established in the following cases:

- after the delivery, if mother decided not to nurse the child, or when feeding by a breast is contraindicated to mother or the child for the medical reasons;

- after the birth of a dead fruit or abortion.

Treatment of giperprolaktinemichesky states. The disturbances connected with a giperprolaktinemiya including amenorrheas, oligomenorrheas, anovulation and a galactorrhoea. Treatment of patients with prolaktinsekretiruyushchy adenomas of a hypophysis (micro and makroprolaktinoma), an idiopathic giperprolaktinemiya or a syndrome of a "empty" Turkish saddle with the accompanying giperprolaktinemiya which are the main morbid conditions causing above-mentioned clinical manifestations.

Route of administration and doses:

Kaberlin 0,5 is intended for oral administration.  As in clinical trials Kaberlin 0,5 applied preferential together with food, and so portability of this class of medicines at reception with food improves, drug is recommended to be accepted during food at all therapeutic indications.

Inhibition/suppression of a physiological lactation. Kaberlin 0,5 it is necessary to apply during the first day after the delivery. The recommended therapeutic dose makes 1 mg (2 tablets on 0,5 mg), accepted once. For suppression of a lactation which was already established the recommended therapeutic mode of dosing makes 0,25 mg (1/2 tablets on 0,5 mg) everyone 12 чв a current of 2 days (the general dose - 1 mg). Such mode of dosing is better transferred by the women who decided to suppress a lactation than reception in the form of a single dose, and it is followed by the smaller frequency of emergence of the undesirable phenomena, especially symptoms of arterial hypotension.

Treatment of giperprolaktinemichesky states. The recommended initial dose of drug Kaberlin 0,5 makes 0,5 mg once a week or 1/2 tablets on 0,5 mg 2 times a week (for example, on Monday and Thursday). Increase in a week dose should be carried out gradually, it is desirable to raise it on 0,5 mg a week every month to achievement of an optimum therapeutic effectiveness. Usually therapeutic dose makes 1 mg a week and can fluctuate in the range from 0,25 to 2 mg a week. From giperprolaktinemiy Kaberlin 0,5 applied to treatment of patients in doses up to 4,5 mg a week. The maximum dose of drug should not exceed 3 mg a day.

The week dose of drug can be accepted for 1 time or to divide into two or the bigger number of inclusion in week, depending on portability of drug the patient. If the appointed doses exceed 1 mg a week, it is recommended to divide a week dose into several receptions as portability of drug in the dose exceeding 1 mg at reception by a single week dose was estimated only at several patients.

At increase in a dose it is necessary to conduct examination of the patient for definition of the minimum dose of the drug causing therapeutic effect. After the effective therapeutic mode of dosing will be picked up, it is recommended to carry out regular (monthly) determination of level of prolactin in blood serum as normalization of this level is usually observed within two or four weeks.

After Kaberlin's cancellation 0,5 the giperprolaktinemiya recurrence is usually observed. However at some patients preservation of oppression of level of prolactin within several months was observed. At 23 of 29 women of group of the subsequent observation after the termination of reception of Kaberlin 0,5 ovulatory cycles lasted longer than 6 months.

Patients of advanced age. Experience of use of drug for patients of advanced age is very limited owing to the offered indications for drug use Kaberlin 0,5. Available data confirm lack of extra risk.

Dose decline or termination of treatment. It is necessary to consider expediency of a dose decline or the termination of treatment in the presence at patients:

- drowsiness or cases of sudden backfilling;

- abnormal liver function.

Features of use:

The general. As well as other alkaloids of an ergot, Kaberlin 0,5 patients should apply with care with a serious cardiovascular illness, Reynaud's syndrome, stomach ulcer or gastrointestinal bleedings, with serious mental diseases in the anamnesis.

There are no data on influence of alcohol on portability of a kabergolin.

Symptomatic arterial hypotension can develop at Kaberlin's use 0,5 at any indication.

Liver failure. At the patients with a heavy liver failure undergoing long therapy kabergoliny it is reasonable to consider a question of use of the lowered doses. Unlike healthy volunteers and persons with a liver failure of smaller degree, at patients with heavy abnormal liver functions (a class C on a scale of Chayld-Pyyu) increase in AUC at a single dose of drug in a dose of 1 mg is noted.

Renal failure. Distinctions in pharmacokinetics of a kabergolin at a disease of kidneys of average and heavy degree were not observed. The pharmacokinetics of a kabergolin at patients with an end-stage of a renal failure or at the patients who are on a hemodialysis was not investigated therefore such patients should use drug with care.

Postural hypotension. During Kaberlin's use 0,5 postural hypotension was observed. Therefore it is necessary to apply with care it with drugs which can also reduce arterial pressure.

Fibrosis, cardial valvulopatiya and other critical phenomena. Fibrous and serous inflammations, such as pleurisy, a pleural exudate, pleural fibrosis, pulmonary fibrosis, a pericardis, a pericardiac exudate, the cardial valvulopatiya covering one or more valves (aortal, mitral and tricuspid), or retroperitoneal fibrosis, arise after prolonged use of such ergolinovy derivatives with agonistic activity concerning serotoninovy 5HT2B-receptors as каберголин. In certain cases symptoms and clinical manifestations of a cardial valvulopatiya are facilitated after cancellation of a kabergolin.

It was revealed that the blood sedimentation rate (BSR) at hydrothorax/fibrosis raises above norm. At increase in SOE to the values exceeding norm carrying out a X-ray analysis of a thorax is recommended. After cancellation of a kabergolin at establishment of the diagnosis of pleurisy / pulmonary fibrosis it was reported about improvement of a clinical picture at the patient.

Valvulopatiya was observed at purpose of cumulative doses therefore patients have to be treated by low effective doses. During each visit it is necessary to estimate again a ratio of advantage and risk for the patient for the purpose of definition of expediency of continuation of treatment by Kaberlin 0,5.

Before long-term treatment all patients have to undergo inspection of cardiovascular system, including an ekhokardiogramma, for definition of existence of an asymptomatic disease of valves. It is also reasonable to carry out definition of basic indicators of the SOE level or other markers of an inflammation, pulmonary function (a X-ray analysis of bodies of a thorax) and function of kidneys prior to treatment. It is unknown whether disease at patients with valve regurgitation can 0,5 worsen Kaberlin's reception. It is established that in the presence of fibrous changes of valves patients should not receive treatment by Kaberlin 0,5.

At long-term treatment: as fibrous disturbances can have the hidden beginning, it is necessary to carry out regular monitoring of possible signs of progressing of fibrosis. Therefore, at treatment it is necessary to pay attention to the following symptoms:

-  plevropulmonalny diseases, such, as диспноэ, short wind, constant cough or thorax pain;

-  a renal failure or obstructions of ureteric/belly vessels which can be shown by pain in a waist/side and hypostasis of the lower extremities, and also any educations in an abdominal cavity or morbidity that can indicate retroperitoneal fibrosis;

-  heart failure: cases of valve or pericardiac fibrosis are often shown in the form of heart failure. Therefore at emergence of the corresponding symptoms it is necessary to exclude valve fibrosis (and a konstriktorny pericardis). Clinical diagnostic monitoring of development of fibrous frustration is obligatory. The first echocardiography has to be carried out within 3-6 months after an initiation of treatment; further the frequency of echocardiographic inspections has to be defined according to individual clinical signs, special attention needs to be paid on above-mentioned symptoms, but monitoring has to be carried out at least each 6-12 months.

Kaberlin's use 0,5 should be stopped at identification on an ECG of signs new or deterioration in the existing valve regurgitation, restriction of the valve or consolidation of shutters of the valve.

Need of carrying out other clinical inspections (for example, physical inspection, auscultation, a X-ray analysis, KT-scanning) has to be defined individually.

The corresponding additional researches, such as determination of the SOE level and serumal creatinine, it is necessary to carry out in need of confirmation of the diagnosis of fibrous disturbances.

Arterial hypotension. Within 6 hours after Kaberlin's use 0,5 symptomatic hypotension therefore with extra care it is necessary to appoint Kaberlin 0,5 along with other medicines which can reduce arterial pressure can develop. Considering an elimination half-life, the hypotensive effect can remain within several days after drug withdrawal. During the first 3-4 days after the beginning of therapy it is recommended to carry out monitoring with regular measurement of arterial pressure. It was reported that in researches of a puerperal period cases of a lowering of arterial pressure were noted (> 20 mm of mercury. systolic and> 10 mm of mercury. diastolic) in 3-4 days after reception of a single dose of a kabergolin of 1 mg. Undesirable effects were usually observed within the first two weeks then their manifestations decreased or at all disappeared.

Disturbance of pulse management. It is necessary to watch carefully patients regarding emergence of disturbances of pulse management. Patients and their environment should be warned about possible changes in behavior which demonstrate disturbance of pulse management, such as pathological azartnost, increase a libido, hyper sexuality, impulsive desire to carry out purchase, an impulsive overeating at use of dopamine agonists, including каберголин. In this case it is necessary to reduce a dose or to stop administration of drug.

Inhibition/suppression of a physiological lactation. As well as other alkaloids of an ergot, Kaberlin 0,5 patients should apply with the arterial hypertension caused by pregnancy only in cases when the expected advantage of treatment exceeds risk.

It is necessary to avoid single use of a dose of 0,25 mg when feeding by a breast, in order to avoid development of postural hypotension.

Treatment of a giperprolaktinemiya. The main reason for a giperprolaktinemiya has to be investigated prior to treatment by Kaberlin 0,5 as the giperprolaktinemiya which is followed by an amenorrhea/galactorrhoea and infertility can be connected with hypophysis tumors.

At achievement of an effective therapeutic dose control of level of prolactin in blood serum is recommended to be exercised once a month, normalization of level of prolactin in serum is observed usually within 2-4 weeks.

After Kaberlin's cancellation 0,5 the giperprolaktinemiya recurrence is usually observed. However at some patients permanent oppression of level of prolactin was observed for several months.

Before an initiation of treatment of a giperprolaktinemiya it is necessary to carry out diagnosis of a condition of a hypophysis. Drug recovers an ovulation and fertility at women with a giperprolaktinemichesky hypogonadism therefore the test for pregnancy is recommended to spend each 4 weeks during the period of an amenorrhea and every time after recovery of periods if their delay makes more than 3 days. Women who do not wish to become pregnant have to apply means of mechanical contraception during therapy and after drug withdrawal before return of anovulation. If pregnancy occurs during treatment, Kaberlin's reception 0,5 should be stopped. As a precautionary measure it is necessary to exercise supervision of women who became pregnant, for identification of signs of increase in a hypophysis as there is a possibility of increase in volume of already existing hypophysis tumor during pregnancy. Before purpose of drug it is necessary to exclude pregnancy. Considering limited clinical experience of use of drug and its long elimination half-life, as a measure of restraint it is recommended to stop to the women planning pregnancy after achievement of a regular ovulatory cycle Kaberlin's use 0,5 a month before the expected conception. For the patients accepting drug it is long, it is recommended to conduct regular gynecologic examinations, including cytologic researches of a neck of uterus and an endometria.

Drowsiness / sudden backfilling. Kaberlin 0,5 can cause drowsiness. Agonists of a dopamine can be the cause of sudden backfilling at patients with Parkinson's disease. Above-mentioned information needs to be given patients and to advise to be careful during control of vehicles or during the work with other automated systems a current of the period of treatment by Kaberlin 0,5. Patients at whom drowsiness and/or episodes of sudden backfilling were observed should abstain from control of vehicles or work with other automated systems. For such patients it is necessary to consider expediency of a dose decline or the termination of treatment.

Another. This medicine contains lactose. Patients with hereditary intolerance of a galactose, deficit of lactase or malabsorption of a glyukozo-galactose should not use this drug.

Ability to influence speed of response at control of motor transport or work with other mechanisms. During the first days of use of a kabergolin of patients it is necessary to warn against participation in the activity demanding bystry and exact reactions.

Patients who are treated kabergoliny and at whom drowsiness and/or sudden episodes of backfilling is noted are recommended to refrain from control of motor transport and the activity requiring special attention, so far such episodes and drowsiness will not disappear.

Children. Safety and efficiency of drug at patients aged up to 16 years were not studied.

Pregnancy and period of feeding by a breast. Pregnancy. Adequate and well controlled researches of use of a kabergolin to pregnant women were not conducted. Researches on animals showed lack of teratogenic effect, however was reported about decrease in fertility and embriotoxity, connected with pharmakodinamichesky activity.

It was reported about cases of emergence of big inborn malformations or the premature termination of pregnancy after therapy kabergoliny pregnant women. Skeletal and muscular pathologies and cardiopulmonary anomalies were the most widespread neonatal anomalies. Data on perinatal disturbances and on further development of babies after pre-natal influence of a kabergolin are absent. According to the available publications, prevalence of big inborn malformations in the general population makes 6,9% or above. Frequency of inborn anomalies varies in different populations. To define precisely whether there is an increased risk it is impossible.

It is necessary to exclude pregnancy before reception of a kabergolin and to avoid pregnancy within not less than one month after the end of therapy. As at patients with a giperprolaktinemiya the elimination half-life of a kabergolin makes 79-115 hours, after establishment of a regular ovulatory cycle of the woman which want to become pregnant, have to stop accepting Kaberlin 0,5 in one month prior to the planned fertilization. It will prevent possible influence of funds for a fruit and does not prohibit a possibility of fertilization as in certain cases the ovulatory cycle remains within six months after drug withdrawal. If fertilization happened during treatment, it is necessary to stop therapy after confirmation of pregnancy for the purpose of restriction of influence of funds for a fruit.

After cancellation of a kabergolin it is necessary to use contraception within not less than 4 weeks. Kabergolin recovers an ovulation and fertility at women with a giperprolaktinemichesky hypogonadism: so that pregnancy can happen to recovery of a menstrual cycle it is recommended to carry out the test for pregnancy during the amenoreyny period after the periods renewed - every time when the periods are postponed more than for three days. Women who do not want to become pregnant are recommended to apply effective non-hormonal contraception during treatment and after cancellation of a kabergolin. Because of a long elimination half-life and limited experience of safety of influence of a kabergolin on a fruit, fertilization is recommended to women who plan pregnancy at least in a month after the termination of reception of a kabergolin. After approach of pregnancy of the woman have to be under observation for the purpose of identification of signs of increase in a hypophysis as during pregnancy growth of the existing hypophysis tumors can be observed.

Feeding by a breast. Because of ability to suppress a lactation Kaberlin 0,5 women cannot apply with giperprolaktinemichesky disturbances ready to nurse.

Kaberlin 0,5 and/or his metabolites were allocated in milk at a research on rats. Information on allocation in breast milk of people does not exist; however, women should not recommend to nurse in case of inefficiency of suppression of a lactation by means of a kabergolin.

Side effects:

In general the undesirable phenomena depend on a drug dose. At patients with the known intolerance of dofaminergichesky drugs the probability of emergence of the undesirable phenomena can be reduced if to begin treatment with drug Kaberlin 0,5 with the lowered doses, for example, of 0,25 mg once a week with the subsequent their gradual increase to achievement of a therapeutic dose. In case of steady or heavy by-effects the temporary dose decline with the subsequent, its more gradual increase, for example, on 0,25 mg/week each 2 weeks, can improve portability of drug.

During treatment drug Kaberlin 0,5 observed and reported side below-mentioned reactions with such frequency: very often> 1/10; often:> 1/100 and <1/10; infrequently> 1/1000 and <1/100; seldom> 1/10000 and <1/1000; very seldom <1/10000; frequency is unknown (it is impossible to estimate on the basis of the available data).

General data. From vascular system. Often: Kabergolin in general causes hypotensive effect in the patients receiving prolonged treatment; postural arterial hypotension; inflows. Infrequently: peripheral vasospasm, loss of consciousness.

From a musculoskeletal system and connecting fabric: infrequently: spasms in legs; seldom: weakness in muscles.

From skin and hypodermic fabrics. Infrequently: skin reactions, for example, alopecia, itch, rash. Seldom: allergic skin reactions.

Laboratory researches. Nechasto:u of women with an amenorrhea observed decrease in level of hemoglobin within the first several months after periods.

Giperprolaktinemichesky states. From mentality: often: depression, sleep disorder;

Frequency is unknown: aggression, hyper sexuality, pathological addiction to gamblings, increase in a libido.

From a nervous system: very often: dizziness / вертиго, headache; infrequently: paresthesia; frequency is unknown: sudden backfilling, syncope.

From the alimentary system: very often: abdominal pain, dyspepsia, gastritis, nausea; often: lock, vomiting.

From reproductive system and mammary glands: often: mammary gland pain.

General disturbances: very often adynamy, increased fatigue.

Inhibition/suppression of a lactation. From a nervous system: often: dizziness / вертиго, headache, drowsiness; infrequently: to a syncope.

From cardiovascular system: very often: defeats of valves of heart (including regurgitation) and related frustration (a pericardis and an exudate in a pericardium cavity).

Interaction with other medicines:

Simultaneous use of drug Kaberlin 0,5 with other medicines, especially with ergot alkaloids, in a puerperal period was not associated with explicit interactions which changed efficiency and safety of this drug. In spite of the fact that there are no data on interaction of a kabergolin with other alkaloids of an ergot, simultaneous use of these drugs during prolonged treatment by Kaberlin 0,5 is not recommended.

As Kaberlin 0,5 realizes the therapeutic action by direct stimulation of dopamine receptors, its combined use with antagonists of dopamine receptors (for example, fenotiazina, phenyl propyl ketones, thioxanthenes and Metoclopramidum) is not recommended as these drugs can reduce prolactin - the lowering effect of a kabergolin.

As well as other derivatives of an ergot, Kaberlin 0,5 it is not necessary to apply with makrolidny antibiotics (for example, erythromycin) in connection with increase in system bioavailability of a kabergolin

Contraindications:

• Hypersensitivity to a kabergolin, other alkaloids of an ergot or to any component of drug.
• Existence in the anamnesis of a fibrous disease of lungs, pericardium and retroperitoneal space.
• Liver failure and toxaemia of pregnant women.
• Simultaneous use of antipsychotic medicines.
• At prolonged treatment: signs of defeat of valves of heart, decide on the help of an echocardiography prior to treatment.
• Puerperal AG or uncontrollable arterial hypertension.
• Preeclampsia, eclampsia.
• Psychosis in the anamnesis or risk of development of puerperal psychosis.

Overdose:

Symptoms of overdose can be similar to those which result from excessive stimulation of dopamine receptors (for example, nausea, vomiting, complaints to stomach aches, postural hypotension, confusion consciousness/psychosis or hallucinations). In case of need it is necessary to apply the supporting measures to removal of any remains of not absorbed drug and maintenance of arterial pressure. Besides, there can be reasonable an administration of drugs of group of antagonists of dopamine.

Storage conditions:

To store at a temperature not above 30 °C. To store in the place, unavailable to children. A period of validity - 2 years. Medicine cannot be used after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 2 tablets in planimetric bezjyacheykovy packaging from aluminum foil. 1 planimetric bezjyacheykovy packaging together with a leaf insert is placed in a pack from a cardboard.