AGALATES
Active material: Kaʙergolin
When ATH: G02CB03
CCF: The inhibitor of prolactin secretion
ICD-10 codes (testimony): D35.2, E22.1, N91
Manufacturer: IVAX Pharmaceuticals s.r.o. (Czech Republic)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Pills white, flat, Oval, with a facet and Valium on one party, Engraved “0.5” on the one hand from risks and “CBG” with another.
| 1 tab. | |
| cabergoline | 500 g |
Excipients: lactose, L-leucine, magnesium stearate (Agent: e572).
2 PC. – vials of dark glass (1) – packs cardboard.
8 PC. – vials of dark glass (1) – packs cardboard.
Pharmacological action
Dopamine receptor agonist. Kaʙergolin – synthetic alkaloid of ergot, jergolina derivative, long-acting dopamine agonist, inhibits the secretion of prolactin. The mechanism of action of kabergolina includes stimulation of Central dopaminovykh receptors in the hypothalamus. In doses higher, than required to suppress the secretion of prolactin, the drug causes the Central dopaminergicheskij effect, due to the stimulation of dopaminovykh D2-receptors. The drug is dozozawisimy nature. Reduction of prolactin in the blood usually is a 3 h and maintained for a 2-3 weeks, Hence to suppress the secretion of milk is usually sufficient taking one dose. When treating giperprolaktinemii prolactin content in the blood to normal through 2-4 weeks of preparation in effective dose. Normal levels of prolactin can persist for several months after drug withdrawal.
Cabergoline has vysokoselektivnym action and does not affect the basal secretion of other hormones of the pituitary and cortisol. Sole farmakodinamicheskim effect, not related to therapeutic effect, is the reduction of HELL. Maximum gipotenzivny effect usually develops through 6 h after a single dose; the degree of reduction of incidence of ad and gipotenzivnogo effect dozozawisima.
Pharmacokinetics
Absorption
After intake of rapidly absorbed from the digestive tract cabergoline. Cmax plasma levels achieved after 0.5-4 no. Food does not affect absorption or distribution kabergolina.
Pharmacokinetics is linear up to a dose 7 mg / day.
Distribution
Linking kabergolina (at concentrations 0.1-10 ng / ml) blood plasma is 41-42%.
Metabolism
In the urine detected metabolites kabergolina: 6-allyl 8β-carboxy-jergolin in quantity 4-6% of the dose, as well as three other metabolita with General content less 3%.
All metabolites to a much lesser extent (compared to kabergolinom) inhibit secretion of prolactin.
Deduction
Cabergoline has long T1/2. T1/2 in healthy volunteers is 63-68 no, T1/2 patients with giperprolaktinemiei is 79-115 no. With this T1/2 equilibrium state is achieved through 4 of the week.
In the urine and feces was found, respectively, 18% and 72% of the dose. The content unmodified kabergolina in urine is 2-3%.
Testimony
-Suppresses physiological lactation postpartum (only medically necessary);
-Suppresses already established lactation (only medically necessary);
— violations, associated with giperprolaktinemiei (including functional disorders such as amenorrhea, spanomenorrhea, anovulation, galactorrhea);
— prolaktinsekretiruûŝie pituitary adenoma (Micro- and makroprolaktinomy);
-idiopathic hyperprolactinemia.
Dosage regimen
Cabergoline is inside, preferably at meal times.
At treatment of irregularities, associated with giperprolaktinemiei, The recommended starting dose is 500 micrograms per week in 1 or 2 admission (eg, in the Monday and Thursday). The dose is increased gradually, usually 500 mcg per week at intervals of 1 month to achieve an optimal therapeutic effect. Maintenance dose – 1 mg / week (0.25-2 mg / week); in some cases, patients with giperprolaktinemiei – to 4.5 mg / week.
If you are using the drug in doses above 1 mg / week, It is recommended that you divide the weekly dose 2 or more receptions depending on portability.
To Suppression of lactation the recommended dose – 1 mg once within the first 24 hours after the birth of a child.
Bearing in mind the indications, experience of application of kabergolina u elderly patients limited. Available data indicate that there is a specific risk.
Side effect
Unwanted effects typically depend on the dose and decrease when it is gradually decreasing.
Suppression of lactation: adverse effects develop about 14% patients. The most frequent: decrease in blood pressure (12%), dizziness (6%) and headache (5%). In long-term care, the frequency of these effects increases to 70%.
The frequency of adverse reactions is represented by the following gradation: often (≥1/100, <1/10), sometimes (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000).
From the nervous system: often – depression, headache and dizziness, paresthesia, feeling tired, drowsiness.
Cardio-vascular system: often – lower HELL, frequency of heartbeat and chest pain; sometimes – nosebleeds; rarely – swoon.
From the digestive system: nausea, vomiting, gastralgia, gastritis, constipation; rarely – abnormal liver function.
Skin and subcutaneous tissue: often – facial flushing.
On the part of the organ of vision: sometimes – hemianopsia.
On the part of the musculoskeletal system: rarely – cramps in the fingers and gastrocnemius muscles.
Allergic reactions: rarely – skin rash.
Lowering blood pressure (systolic more than 20 mm Hg. Article. and diastolic more than 10 mm Hg. Art.) observed through 3-4 the day after receiving a single dose of kabergolina 1 mg in women after childbirth.
Adverse effects usually develop during the first two weeks, then decrease or disappear. Cancel the drug in connection with side-effect was required in 3% cases.
Postmarketingovoe monitoring
Treatment kabergolinom accompanied by excessive daytime sleepiness and sudden episodes of sleep, particularly in patients with Parkinson's disease.
There are reports of increasing libido in patients with Parkinson's disease when treatment dopamine agonists, including cabergoline, especially in high doses. Also in the treatment of kabergolinom marked pleural exudate, plyevralinyi fibrosis, valvulopatyya, respiratory disorders (incl. respiratory insufficiency).
Contraindications
-Postpartum or uncontrolled arterial hypertension;
- Severe liver;
-unwanted effects from the light, such as pleuritis or fibrosis (incl. history), associated with taking dopamine agonists;
— psychosis (incl. history) or risk their development;
-pregnancy and developed on its background pre-eclampsia and eclampsia;
- Lactation (breast-feeding);
-hypersensitivity to kabergolinu, other alkaloids lpv or any of the preparation components.
The efficacy and safety of kabergolina in children under 16 years has not been studied.
FROM caution should designate product in patients with cardiovascular disease, hypotension, Raynaud's syndrome, peptic ulcers or gastrointestinal bleeding, in patients with end stage renal failure or in gemodialise, elderly patients.
Pregnancy and lactation
The drug is contraindicated in pregnancy and lactation (breast-feeding).
Before you start taking the drug should be deleted pregnancy. You are advised to avoid pregnancy for at least 1 months after the end of treatment. There are limited data on the admission of drugs in pregnancy, received during the first 8 weeks after conception. Application of kabergolina has not been accompanied by an increased risk of abortion, preterm birth, multiple pregnancy or birth of violations. Other data has been received so far.
IN experimental studies animals direct or indirect adverse effects on kabergolina during pregnancy, development of the embryo / fetus, birth or postnatal development not detected.
Given the limited experience with the application of kabergolina during pregnancy, When it is planning a drug should be lifted. In the case of pregnancy during treatment with cabergoline immediately cancelled. In connection with the possibility of expansion of pre-existing tumors should be monitored for signs of increase in the pituitary gland in pregnant women.
Since cabergoline suppresses lactation, the drug should not be appointed to mothers, who prefer breastfeeding of infants. At the time of treatment should stop breastfeeding kabergolinom.
Cautions
To open the bottle, First, click on the cover, then turn it, as shown on the cover. Capsule with silica gel from bottles do not extract and ingest.
Data on the efficacy and safety of kabergolina in patients with liver or kidney disease are limited. Pharmacokinetics of kabergolina did not significantly change when moderate or severe renal insufficiency, has not been studied in patients with end stage renal failure or in gemodialise. Therefore, in these patients, the drug should be used with caution.
The effects of alcohol on the overall portability of kabergolina is not installed.
Cabergoline can cause symptomatic hypertension hypotension, especially when coupled with drugs, lower blood pressure. It is recommended to regularly measure the HELL in the first 3-4 days after initiation of treatment.
Hyperprolactinemia in conjunction with amenorrhea and infertility can be associated with tumors of the pituitary gland, Therefore, before starting treatment kabergolinom you need to find out why giperprolaktinemii.
It is recommended to check the content of prolactin in the blood serum of each month, Since the achievement of an effective therapeutic modes normal prolactin level is maintained for 2-4 weeks.
After the drug giperprolaktinemia usually occurs again. However, in some patients, there has been a steady decline in the concentration of prolactin in the months.
Cabergoline restores ovulation and fertility in women with giperprolaktinemicheskim hypogonadism. Because pregnancy can occur before the resumption of menstruation, pregnancy tests are recommended during the period of amenorrhea, and after the restoration of the menstrual cycle – in all cases, delays of more than 3 day. Women, who do not want to get pregnant, It is recommended to apply effective non-hormonal contraception during treatment and after the kabergolinom. Women, planning pregnancy, It is recommended that you conceive no earlier than 1 a month after the drug. A number of patients ovuljatornyj cycle was maintained during the 6 months after drug withdrawal.
With long-term use, kabergolina, as with other ergot derivatives, pleural exudate may appear/pulmonary fibrosis and heart valve lesions. Sometimes these phenomena were observed in patients, previously treated with agonists of dopamine from the Group of ergot. Cancel kabergolina in the case of specified pathology resulted in improving the condition of the patient.
When new clinical symptoms of the respiratory system, it is recommended that lung roentgenoscopy. In patients with plevral'nymi vypotami/fibrosis noted increased ESR, in this connection, elevated ESR without obvious clinical signs should also conduct x-ray examination.
When you use kabergolina may appear drowsy and episodes of sudden sleep, particularly in patients with Parkinson's disease. Sudden falling asleep during daily activities, developing in some cases without the forerunners, notes are rarely.
The drug contains lactose. Patients with rare hereditary form of galactose intolerance, lactase deficiency, or in violation of the glucose-Galactose malabsorption should not take cabergoline.
Effects on ability to drive a car and use machines
Cabergoline reduces ad, that may interfere with the speed of response in some patients. This should be taken into account in situations, requiring concentration of attention, such as driving a car or control mechanisms. Patients should be informed about the necessity to observe caution when driving or management mechanisms.
Patients, have already experienced drowsiness and/or sudden episodes of falling asleep in the treatment of kabergolinom, should abandon driving or other, risk-related activity, when violations of reaction rate can represent for them and other people risk serious injury or death. Sometimes it is advisable to decrease the dosage or removal from the market.
Preclinical safety data
As shown in preclinical studies, cabergoline is safe in a large range of doses and teratogenic, mutagenic or carcinogenic effect.
Overdose
Information about overdose no. Based on the results of animal experiments, You can expect the emergence of symptoms, caused hyperstimulation dopaminovykh receptors: nausea, vomiting, decrease in blood pressure, human consciousness/psychosis or hallucinations.
Treatment: According to rehabilitation measures should be made HELL. Besides, When expressed symptoms of the central nervous system (hallucinations) You may want to use dopamine antagonists.
Drug Interactions
Effect of macrolide antibiotics on plasma kabergolina when sharing is not known. Considering the possibility of increasing the level of kabergolina, the drug is not recommended for use in combination with macrolide.
The mechanism of action of kabergolina is associated with direct stimulation of dopaminovykh receptors, Therefore, it should not be used in combination with dopaminovykh receptors antagonists (fenotiazinы, butyrofenonы, tïoksantenı, metoclopramide).
There is no information about the interaction of kabergolina with other ergot alkaloids, Nonetheless, not recommended for prolonged use of such a combination.
Given the pharmacodynamic properties of kabergolina (gipotenzivne effect), It is necessary to take into account the interaction with drugs, lower blood pressure.
In clinical studies in patients with Parkinson's disease with levodopa interactions or pharmacokinetic selegilinom not detected.
Pharmacokinetic interaction with other drugs on the basis of available information on the metabolism of kabergolina cannot be predicted.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored in a dry, reach of children, in tightly closed original bottle at a temperature of no higher than 30° c. Shelf life – 2 year.
