Dostinex
Active material: Kaʙergolin
When ATH: G02CB03
CCF: The inhibitor of prolactin secretion
ICD-10 codes (testimony): D35.2, E22.1, N91
When CSF: 15.07.08.01.01
Manufacturer: PFIZER ITALIA S.r.L. (Italy)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Pills white, flat, oblong; marked with letters “P” and “In”, separated by notch, on the one hand and the numeral “700” with short incisions on the top and bottom numbers – with another.
| 1 tab. | |
| cabergoline | 500 g |
Excipients: leucine, lactose bezvodnaya.
2 PC. – vials of dark glass (1) – packs cardboard.
8 PC. – vials of dark glass (1) – packs cardboard.
Pharmacological action
Dopamine receptor agonist. Kaʙergolin – dopaminergicescoe derivative èrgolina, characterized by a pronounced and prolonged prolaktinsnižaûŝim action. The mechanism of action is related to the direct stimulation of dopaminovykh D2-laktotropnyh receptor cells of the pituitary gland. At doses, exceeding such to reduce prolactin plasma, provides central dopaminergicescoe effect, resulting from the stimulation of dopaminovykh D2-receptors.
Reduction of prolactin in the blood plasma through 3 h after administration Dostineksa® and maintained for a 7-28 days in healthy volunteers and patients with giperprolaktinemiei and to 14-21 day – women in the postpartum period. Prolaktinsnižaûŝee effect is dose-dependent, both in relation to manifestation, and duration of action.
Cabergoline has strictly electoral action and, Consequently, has no effect on basal secretion of other hormones of the pituitary gland, as well as cortisol.
The pharmacological effects of kabergolina, not related to therapeutic effect, declining AD. The one-time drug gipotenzivny maximum effect is observed during the first 6 h and is reversible.
Pharmacokinetics
Absorption
After intake of rapidly absorbed from the digestive tract cabergoline. Cmax plasma achieved through 0.5-4 no. Eating does not affect the absorption and distribution of kabergolina.
Distribution
Css achieved through 4 weeks of therapy because of the long half-life. Binding to plasma proteins is 41-42%.
Metabolism
The main product of the metabolism of kabergolina, identified in urine, is 6-allyl-8β-carboxy-èrgolin in concentrations up to 4-6% of the dose. Content in the urine 3 additional metabolites does not exceed 3% of the dose. Metabolic products have significantly less effect against suppression of secreting prolactin as compared to kabergolinom.
Deduction
T1/2, ranked by rate with urine, is 63-68 h in healthy volunteers and 79-115 h patients with giperprolaktinemiei.
Through 10 days after the use of the drug in the urine and feces are found respectively 18% and 72% of the dose, proportion of unchanged drug in urine is 2-3%.
Testimony
-Prevention of physiological post-lactation;
-Suppression of the post-lactation established;
-treatment of, associated with giperprolaktinemiei, including functional disorders, as amenorrhea, spanomenorrhea, Anovulation, and galactorrhea;
— prolaktinsekretiruûŝie pituitary adenoma (Micro- and makroprolaktinomy), idiopathic hyperprolactinemia or syndrome “blank” Sella turcica in conjunction with giperprolaktinemiei.
Dosage regimen
Dostineks® It should be taken into, preferably at mealtimes.
To to prevent lactation prescribed drug dose 1 mg (2 tab.) Once on the first day after birth.
To suppress established lactation appoint 0.25 mg (1/2 tab.) 2 times / day for 2 days (the total dose is equal to 1 mg). To reduce the risk of orthostatic hypotension lactating patients have single dose Dostineksa® should not exceed 0.25 mg.
To the treatment of, associated with giperprolaktinemiei, the drug is prescribed in a dose 0.5 mg per week 1 or 2 admission (by 1/2 tab., eg, in the Monday and Thursday). Increasing weekly dose should be gradually – on 0.5 mg at intervals of 1 months to achieve an optimal therapeutic effect. Average therapeutic dose is 1 mg per week, but may vary in range from 0.25 mg 2 mg per week. The maximum dose for patients with giperprolaktinemiei is 4.5 mg per week.
Depending on the portable weekly dose can be taken once or divided into 2 or more receptions in week. Division-week dose by a number of techniques recommended when prescribing the drug in a dose of 1 g per week.
In patients with hypersensitivity to drugs dopaminergičeskim the likelihood of side effects can be reduced, starting therapy Dostineksom® in the lower dose (by 0.25 mg 1 once a week), followed by a gradual increase to achieve her therapeutic dose. To improve the acceptability of the drug when an expressed side effects may temporarily reduce the dose followed by a gradual increase in its, eg, on 0.25 mg a week every 2 of the week.
Side effect
In clinical studies using Dostineksa® to prevent and suppress physiological lactation were observed side-effects of approximately 14% Women; When treating violations, associated with giperprolaktinemiei, frequency of adverse reactions was 68%.
Adverse events occurred, primarily, during the first two weeks of therapy, and in most cases disappear as therapy or within a few days after the cancellation Dostineksa®. On the severity of side effects were weakly or moderately expressed and dozozawisimy nature. At least, Once in the course of therapy, severe side effects were observed in 14% patients; due to the side effects of the treatment have been discontinued 3% patients.
Cardio-vascular system: heartbeat; rarely – orthostatic hypotension (with long-term use, gipotenzivne); asymptomatic decline ad during the first 3-4 days postpartum (systolic – more than 20 mmHg., diastolic – more than 10 mmHg.).
From the digestive system: nausea, vomiting, epigastric pain, abdominal pain, constipation, gastritis, dyspepsia.
From the central and peripheral nervous system: dizziness/vertigo, headache, fatigue, drowsiness, depression, asthenia, paresthesia, fainting.
Laboratory findings: in women with amenorrhea reduced hemoglobin in the first months after the restoration of menstruation.
Other: mastodinija, nose bleed, “tides” of blood to the skin of the face, tranzitornaya hemianopsia, spasms of blood vessels of the fingers, cramping of the muscles of the lower extremities.
With long-term therapy with the use of Dostineksa® deviation from the norm of standard laboratory parameters was observed rarely; in women with amenorrhea reduced hemoglobin was observed during the first few months after the restoration of menstruation.
In postmarketingovom the study registered the following adverse reactions, associated with the use of cabergoline: alopecia, increased activity of CPK in the blood, mania, dyspnoea, swelling, fibrous, abnormal liver function, abnormalities in liver function tests, hypersensitivity reactions, rash, respiratory disorders, respiratory insufficiency, valvulopatyya.
Contraindications
- Childhood and adolescence up 16 years (Safety and efficacy have not been established);
-hypersensitivity to kabergolinu or other components of the drug, as well as any alkaloids lpv.
FROM caution the preparation is used to treat hypertension, advanced in pregnancy (preэklampsiya, Postpartum hypertension), severe cardiovascular diseases, Raynaud's syndrome, peptic ulcer, gastrointestinal bleeding, severe hepatic insufficiency (recommended lower doses), severe psychotic or cognitive violations (incl. history), symptoms of heart and respiratory dysfunction due to fibrotic changes or availability of such States in history, together with the use of drugs, providing gipotenzivne effect (because of the risk of orthostatic hypotension).
Pregnancy and lactation
Since controlled clinical studies using Dostineksa® in pregnant women has been carried out, application of the drug during pregnancy is possible only in the case, when the intended benefits to the mother outweighs the potential risk to the fetus.
If the pregnancy occurred in the face of treatment Dostineksom®, consideration should be given to preparation, considering the risk/benefit ratio.
Pregnancy should be avoided for, least, 1 months after discontinuation of the drug, because of its long half-life and limited data on the effects on the fetus. According to the information application Dostineksa® dose 0.5-2 mg a week over violations, associated with giperprolaktinemiei, has not been accompanied by an increase in the frequency of miscarriages, preterm birth, multiple pregnancy and congenital malformations.
Information on the allocation of the drug in breast milk is not, However, in the absence of the effect of applying Dostineksa® to prevent or suppress lactation should abandon breastfeeding. When violations, associated with giperprolaktinemiei, Dostineks® do not assign patients, not wishing to stop lactation.
Cautions
Before assigning Dostineksa® with a view to treatment of, associated with giperprolaktinemiei, There is a need to conduct a comprehensive study of the function of the pituitary.
When increasing doses to the patient should be under the supervision of a physician for the purpose of establishing the lowest effective dose, provides therapeutic effect. After the selection of effective dosage recommended for regular (1 Once a month) determination of prolactin in serum. Prolactin level normalization is usually observed during 2-4 weeks of treatment.
After applying Dostineksa® ortostatical gipotenzia can develop. Be wary appoint Dostineks® While therapy drugs, providing gipotenzivne effect.
With long-term therapy Dostineks® should be appointed in lower doses to patients with severe hepatic insufficiency (class C Child-Pugh), which shows a prolonged therapy Dostineksom®. The one-time use of such patients drug dose 1 mg AUC increased compared with healthy volunteers and patients with less pronounced hepatic insufficiency.
After prolonged use of kabergolina patients experienced a pleural effusion/pleural fibrosis and val′vulopatiâ. In some cases, patients received prior therapy èrgotininovymi dopamine agonists. So Dostineks® should be used with caution in patients with existing signs and/or clinical symptoms of cardiac dysfunction (incl. history). After the drug, patients noted an improvement in symptoms as described above.
After the cancellation Dostineksa® usually there is a relapse giperprolaktinemii. However, a number of patients noted persistant suprescia prolactin levels in a few months. Most women have registered ovulâtornye cycles for at least 6 months after the cancellation Dostineksa®.
Dostineks® Restores the ovulation and fertility in women with giperprolaktinemičeskim hypogonadism. Because pregnancy can occur even before the restoration of menstruation, pregnancy tests are recommended at least every 1 times a 4 week during the period of amenorrhea, and after the restoration of menstruation – every time, When there is a delayed menstruation for more than 3 day. Women, who want to avoid pregnancy, during treatment Dostineksom®, as well as after the cancellation Dostineksa® and until the return of Anovulation should use non-hormonal methods of contraception.
Women, whose pregnancy was achieved, should be under the supervision of a physician for the timely detection of symptoms increase pituitary, because during pregnancy may increase the size of the pre-existing pituitary tumors.
The use of kabergolina causes drowsiness. In patients with Parkinson's disease application of dopaminovykh receptors agonists can cause sudden falling asleep. In such cases, it is recommended that you reduce the dose Dostineksa® or discontinue therapy.
Studies on the use of drugs in elderly patients with impaired, associated with giperprolaktinemiei, not performed.
Use in Pediatrics
Safety and efficacy of Dostineksa® in children and adolescents under the age of 16 years not installed.
Effects on ability to drive vehicles and management mechanisms
Patients, host Dostineks®, u are experiencing drowsiness, should be warned that, that they are encouraged to refrain from driving and performance, where reduced attention can create for them or the risk of serious injury or death.
Overdose
Symptoms: nausea, vomiting, dyspeptic disorders, orthostatic hypotension, mental confusion/psychosis or hallucinations.
Treatment: activities should be carried out, to the excretion of nevsosavšegosâ drug (gastric lavage) and maintenance of HELL. Recommended the appointment of dopamine antagonists.
Drug Interactions
There is no information about the interaction of kabergolina and other alkaloids lpv; However, the simultaneous use of these drugs during long-term therapy Dostineksom® not recommended.
Since Dostineks® provides therapeutic effect by direct stimulation of dopaminovykh receptors, the drug cannot be assigned simultaneously with drugs, acting as dopamine antagonists (eg, fenotiazinы, butyrofenonы, tïoksantenı, metoclopramide), tk. the past may reduce the action prolaktinsnižaûŝee Dostineksa®.
Like other ergot derivatives, Dostineks® cannot be used in conjunction with the antibiotic macrolides (eg, erythromycin), because this can lead to increased systemic bioavailability kabergolina.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 2 year.
